Datasets:

reichenbach

/

drug_combi_instruct_test

like 0

4a5a8940cfaed4c9cfd066173390b1dc

A randomized Phase III trial demonstrated noninferiority of APF530 500 mg SC ( granisetron 10 mg ) to intravenous palonosetron 0.25 mg in preventing CINV in patients receiving MEC or HEC in acute ( 0 - 24 hours ) and delayed ( 24 - 120 hours ) settings , with activity over 120 hours .

Biochronomer™ technology and the development of APF530, a sustained release formulation of granisetron. granisetron and other 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are first-line agents for preventing chemotherapy-induced nausea and vomiting (CINV). Current treatment guidelines prefer the longer-acting agent, palonosetron, for CINV prevention in some chemotherapy regimens. A new granisetron formulation, APF530, has been developed as an alternative long-acting agent. APF530 utilizes Biochronomer(™) technology to formulate a viscous tri(ethylene glycol) poly(orthoester)-based formulation that delivers - by single subcutaneous (SC) injection - therapeutic granisetron concentrations over 5 days. The poly(orthoester) polymer family contain an orthoester linkage; these bioerodible polymer systems are specifically designed for controlled, sustained drug delivery. Pharmacokinetics and pharmacodynamics of APF530 250, 500, or 750 mg SC (granisetron 5, 10, or 15 mg, respectively) administered 30-60 minutes before chemotherapy were evaluated in two Phase II trials in cancer patients receiving moderately (MEC) or highly (HEC) emetogenic chemotherapy. Pharmacokinetics were dose proportional, with slow granisetron absorption and elimination. Both trials demonstrated similar results for median half-life, time to maximum concentration, and exposure for APF530 250 and 500 mg, with no differences between patients receiving MEC or HEC. A randomized Phase III trial demonstrated noninferiority of APF530 500 mg SC ( granisetron 10 mg ) to intravenous palonosetron 0.25 mg in preventing CINV in patients receiving MEC or HEC in acute ( 0 - 24 hours ) and delayed ( 24 - 120 hours ) settings , with activity over 120 hours . Mean maximum granisetron plasma concentrations were 10.8 and 17.8 ng/mL, and mean half-lives were 30.8 and 35.9 hours after SC administration of APF530 250 and 500 mg, respectively. Therapeutic granisetron concentrations were maintained for greater than 120 hours (5 days) in both APF530 dose groups. These data suggest that APF530 - an SC-administered formulation of granisetron delivered via Biochronomer technology - represents an effective treatment option for the prevention of both acute and delayed CINV in patients receiving either MEC or HEC.

https://pubmed.ncbi.nlm.nih.gov/27186139/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Biochronomer™ technology and the development of APF530, a sustained release formulation of granisetron. granisetron and other 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are first-line agents for preventing chemotherapy-induced nausea and vomiting (CINV). Current treatment guidelines prefer the longer-acting agent, palonosetron, for CINV prevention in some chemotherapy regimens. A new granisetron formulation, APF530, has been developed as an alternative long-acting agent. APF530 utilizes Biochronomer(™) technology to formulate a viscous tri(ethylene glycol) poly(orthoester)-based formulation that delivers - by single subcutaneous (SC) injection - therapeutic granisetron concentrations over 5 days. The poly(orthoester) polymer family contain an orthoester linkage; these bioerodible polymer systems are specifically designed for controlled, sustained drug delivery. Pharmacokinetics and pharmacodynamics of APF530 250, 500, or 750 mg SC (granisetron 5, 10, or 15 mg, respectively) administered 30-60 minutes before chemotherapy were evaluated in two Phase II trials in cancer patients receiving moderately (MEC) or highly (HEC) emetogenic chemotherapy. Pharmacokinetics were dose proportional, with slow granisetron absorption and elimination. Both trials demonstrated similar results for median half-life, time to maximum concentration, and exposure for APF530 250 and 500 mg, with no differences between patients receiving MEC or HEC. A randomized Phase III trial demonstrated noninferiority of APF530 500 mg SC ( granisetron 10 mg ) to intravenous palonosetron 0.25 mg in preventing CINV in patients receiving MEC or HEC in acute ( 0 - 24 hours ) and delayed ( 24 - 120 hours ) settings , with activity over 120 hours . Mean maximum granisetron plasma concentrations were 10.8 and 17.8 ng/mL, and mean half-lives were 30.8 and 35.9 hours after SC administration of APF530 250 and 500 mg, respectively. Therapeutic granisetron concentrations were maintained for greater than 120 hours (5 days) in both APF530 dose groups. These data suggest that APF530 - an SC-administered formulation of granisetron delivered via Biochronomer technology - represents an effective treatment option for the prevention of both acute and delayed CINV in patients receiving either MEC or HEC. ### Response: granisetron, palonosetron

ef4fb4cd54c88e22cd1b882061876c8d

Classical NSAIDs are still the most logical choice for agents that will slow the progression or delay the onset of AD and other neurodegenerative diseases despite failures of naproxen , celecoxib and rofecoxib in AD clinical trials .

Non-steroidal anti-inflammatory drugs (NSAIDs) and other anti-inflammatory agents in the treatment of neurodegenerative disease. Inflammation is characteristic of a broad spectrum of neurodegenerative diseases. These include Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases, amyotrophic lateral sclerosis, all of the tauopathies, multiple sclerosis and many other less common conditions. Morphologically, the level of inflammation is determined by the concentration and degree of activation of microglial cells. Biochemically, it is judged by the presence of a spectrum of inflammatory mediators. Epidemiological evidence indicates that anti-inflammatory agents such as non-steroidal anti-inflammatory drugs (NSAIDs) have a sparing effect on AD and PD indicating that inflammation exacerbates the pathology in these diseases. NSAIDs are protective in transgenic animal models of AD, providing further evidence of the negative consequences of inflammation. Here we describe an in vitro model, which was used to study the protective effects of NSAIDs in AD. This model is based on neuronal cell killing by stimulated microglia or microglia-like cells. In this model NSAIDs show protective effects at a therapeutically relevant level, which is in the low micromolar range. There are reports suggesting that NSAIDs act independently of cyclooxygenase (COX) inhibition, but only at higher doses. Classical NSAIDs are still the most logical choice for agents that will slow the progression or delay the onset of AD and other neurodegenerative diseases despite failures of naproxen , celecoxib and rofecoxib in AD clinical trials . Several other classes of anti-inflammatory drugs have been identified as potentially beneficial in this and similar assay systems. Therefore combination therapy with other anti-inflammatory agents that work through different mechanisms of action might prove to be a superior therapeutic strategy.

https://pubmed.ncbi.nlm.nih.gov/15974901/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Non-steroidal anti-inflammatory drugs (NSAIDs) and other anti-inflammatory agents in the treatment of neurodegenerative disease. Inflammation is characteristic of a broad spectrum of neurodegenerative diseases. These include Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases, amyotrophic lateral sclerosis, all of the tauopathies, multiple sclerosis and many other less common conditions. Morphologically, the level of inflammation is determined by the concentration and degree of activation of microglial cells. Biochemically, it is judged by the presence of a spectrum of inflammatory mediators. Epidemiological evidence indicates that anti-inflammatory agents such as non-steroidal anti-inflammatory drugs (NSAIDs) have a sparing effect on AD and PD indicating that inflammation exacerbates the pathology in these diseases. NSAIDs are protective in transgenic animal models of AD, providing further evidence of the negative consequences of inflammation. Here we describe an in vitro model, which was used to study the protective effects of NSAIDs in AD. This model is based on neuronal cell killing by stimulated microglia or microglia-like cells. In this model NSAIDs show protective effects at a therapeutically relevant level, which is in the low micromolar range. There are reports suggesting that NSAIDs act independently of cyclooxygenase (COX) inhibition, but only at higher doses. Classical NSAIDs are still the most logical choice for agents that will slow the progression or delay the onset of AD and other neurodegenerative diseases despite failures of naproxen , celecoxib and rofecoxib in AD clinical trials . Several other classes of anti-inflammatory drugs have been identified as potentially beneficial in this and similar assay systems. Therefore combination therapy with other anti-inflammatory agents that work through different mechanisms of action might prove to be a superior therapeutic strategy. ### Response: naproxen, celecoxib, rofecoxib

f3c31f04fdf5a6a559c0fd215a4ebe4c

Between 1987 and 2003 , patients 18 years old were given adjuvant chemotherapy consisting of one of two ' paediatric ' regimens ( depending on the time of presentation ) and craniospinal local-boost radiotherapy : regimen A ( n = 12 ) , vincristine ( VCR ) , intrathecal and/or intravenous methotrexate and conventional radiotherapy ; or regimen B ( n = 11 ) sequencing intensive doses of multiple agents followed by hyperfractionated accelerated radiotherapy ( HART ) .

Survival of adults treated for medulloblastoma using paediatric protocols. We retrospectively studied 26 consecutive adults treated for medulloblastoma using paediatric protocols. Between 1987 and 2003 , patients 18 years old were given adjuvant chemotherapy consisting of one of two ' paediatric ' regimens ( depending on the time of presentation ) and craniospinal local-boost radiotherapy : regimen A ( n = 12 ) , vincristine ( VCR ) , intrathecal and/or intravenous methotrexate and conventional radiotherapy ; or regimen B ( n = 11 ) sequencing intensive doses of multiple agents followed by hyperfractionated accelerated radiotherapy ( HART ) . A VCR-lomustine-based maintenance followed both regimens. Three additional patients received a tailored treatment due to their impaired neurological status after surgery. The median age at diagnosis was 26 years (range 18-41 years). With a median follow-up of 46 months, 5-year disease-free and overall survival rates were 65+/-11% and 73+/-10%, respectively, for the series as a whole. All patients who received regimen B (5 of whom had metastatic Chang M2-M3 disease) are alive with no evidence of disease at 39 months. Although the number of patients is limited, our data suggest that the sandwich sequential, moderately intensive chemotherapy in combination with HART is an effective treatment for medulloblastoma in adults, and this approach seems to overcome previously-recognised risk factors.

https://pubmed.ncbi.nlm.nih.gov/15869875/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Survival of adults treated for medulloblastoma using paediatric protocols. We retrospectively studied 26 consecutive adults treated for medulloblastoma using paediatric protocols. Between 1987 and 2003 , patients 18 years old were given adjuvant chemotherapy consisting of one of two ' paediatric ' regimens ( depending on the time of presentation ) and craniospinal local-boost radiotherapy : regimen A ( n = 12 ) , vincristine ( VCR ) , intrathecal and/or intravenous methotrexate and conventional radiotherapy ; or regimen B ( n = 11 ) sequencing intensive doses of multiple agents followed by hyperfractionated accelerated radiotherapy ( HART ) . A VCR-lomustine-based maintenance followed both regimens. Three additional patients received a tailored treatment due to their impaired neurological status after surgery. The median age at diagnosis was 26 years (range 18-41 years). With a median follow-up of 46 months, 5-year disease-free and overall survival rates were 65+/-11% and 73+/-10%, respectively, for the series as a whole. All patients who received regimen B (5 of whom had metastatic Chang M2-M3 disease) are alive with no evidence of disease at 39 months. Although the number of patients is limited, our data suggest that the sandwich sequential, moderately intensive chemotherapy in combination with HART is an effective treatment for medulloblastoma in adults, and this approach seems to overcome previously-recognised risk factors. ### Response: vincristine, methotrexate

7c1b48c4fded5536004f52b2f9c14572

The US Food and Drug Administration ( FDA ) recommends that " concomitant use of drugs that inhibit CYP2C19 ( e.g. , omeprazole ) should be discouraged . " As the presence of PPIs and clopidogrel in plasma is short lived , separation by 12 - 20 h should in theory prevent competitive inhibition of CYP metabolism and minimize any potential , though unproven , clinical interaction .

Proton pump inhibitor and clopidogrel interaction: fact or fiction? Current consensus recommendations state that patients prescribed clopidogrel plus aspirin should receive a proton pump inhibitor (PPI) to reduce gastrointestinal bleeding. clopidogrel is converted to its active metabolite by cytochrome P450 (CYP) enzymes. clopidogrel users with decreased CYP2C19 function have less inhibition of platelet aggregation and increased cardiovascular (CV) events. As PPI metabolism also involves CYP2C19, it was hypothesized that competition by PPIs might interfere with clopidogrel's action. omeprazole, but not other PPIs, worsens surrogate markers of clopidogrel efficacy. Some (but not all) observational studies show that clopidogrel users prescribed PPIs have increased risks of CV events (hazard/odds ratios=1.25-1.5). When effect sizes are small to moderate (relative risks<1.5-2.0), however, it is only possible to conclude whether statistical associations are valid in randomized trials. A randomized trial of omeprazole vs. placebo in clopidogrel users showed no difference in CV events (hazard ratio=1.02,0.70-1.51). Thus, current evidence does not justify a conclusion that PPIs are associated with CV events among clopidogrel users, let alone a judgment of causality. Nonetheless, positive results from some observational studies and biological plausibility have led some health-care providers to accept that PPIs reduce clopidogrel's efficacy. The US Food and Drug Administration ( FDA ) recommends that " concomitant use of drugs that inhibit CYP2C19 ( e.g. , omeprazole ) should be discouraged . " As the presence of PPIs and clopidogrel in plasma is short lived , separation by 12 - 20 h should in theory prevent competitive inhibition of CYP metabolism and minimize any potential , though unproven , clinical interaction . PPI may be given before breakfast and clopidogrel at bedtime, or PPI may be taken before dinner and clopidogrel at lunchtime.

https://pubmed.ncbi.nlm.nih.gov/19904241/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Proton pump inhibitor and clopidogrel interaction: fact or fiction? Current consensus recommendations state that patients prescribed clopidogrel plus aspirin should receive a proton pump inhibitor (PPI) to reduce gastrointestinal bleeding. clopidogrel is converted to its active metabolite by cytochrome P450 (CYP) enzymes. clopidogrel users with decreased CYP2C19 function have less inhibition of platelet aggregation and increased cardiovascular (CV) events. As PPI metabolism also involves CYP2C19, it was hypothesized that competition by PPIs might interfere with clopidogrel's action. omeprazole, but not other PPIs, worsens surrogate markers of clopidogrel efficacy. Some (but not all) observational studies show that clopidogrel users prescribed PPIs have increased risks of CV events (hazard/odds ratios=1.25-1.5). When effect sizes are small to moderate (relative risks<1.5-2.0), however, it is only possible to conclude whether statistical associations are valid in randomized trials. A randomized trial of omeprazole vs. placebo in clopidogrel users showed no difference in CV events (hazard ratio=1.02,0.70-1.51). Thus, current evidence does not justify a conclusion that PPIs are associated with CV events among clopidogrel users, let alone a judgment of causality. Nonetheless, positive results from some observational studies and biological plausibility have led some health-care providers to accept that PPIs reduce clopidogrel's efficacy. The US Food and Drug Administration ( FDA ) recommends that " concomitant use of drugs that inhibit CYP2C19 ( e.g. , omeprazole ) should be discouraged . " As the presence of PPIs and clopidogrel in plasma is short lived , separation by 12 - 20 h should in theory prevent competitive inhibition of CYP metabolism and minimize any potential , though unproven , clinical interaction . PPI may be given before breakfast and clopidogrel at bedtime, or PPI may be taken before dinner and clopidogrel at lunchtime. ### Response: omeprazole, clopidogrel

7639b3ca6251f63f76d161da9c24f217

Long-term overall- and progression-free survival after pentostatin , cyclophosphamide and rituximab therapy for indolent non-Hodgkin lymphoma .

Long-term overall- and progression-free survival after pentostatin , cyclophosphamide and rituximab therapy for indolent non-Hodgkin lymphoma . In a prospective phase II trial, pentostatin combined with cyclophosphamide and rituximab (PCR) induced strong responses and was well-tolerated in previously untreated patients with advanced-stage, indolent non-Hodgkin lymphoma (iNHL). After a median patient follow-up of more than 108 months, we performed an intent-to-treat analysis of our 83 participants. Progression-free survival (PFS) rates at 108 months for follicular lymphoma (FL), marginal zone lymphoma (MZL) and small lymphocytic lymphoma (SLL) were 71%, 67% and 15%, respectively, and were affected by clinicopathological characteristics. Ten-year PFS rates for those with beta-2-microglobulin levels <2·2 and ≥2·2 mg/l prior to treatment were 71% and 21%, respectively. Patients without bone marrow involvement had 10-year PFS rates of 72% vs. 29% for those with involvement. At time of analysis, the median overall survival (OS) had not been reached. The OS rate was 64% at 10 years and differed significantly based on histology: 94% for FL, 66% for MZL and 39% for SLL. Long-term toxicities included 18 (21·7%) patients with second malignancies and 2 (2·4%) who developed myelodysplastic syndrome after receiving additional lines of chemotherapy. Our 10-year follow-up analysis confirms that PCR is an effective, robust and tolerable treatment regimen for patients with iNHL.

https://pubmed.ncbi.nlm.nih.gov/30820940/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Long-term overall- and progression-free survival after pentostatin , cyclophosphamide and rituximab therapy for indolent non-Hodgkin lymphoma . In a prospective phase II trial, pentostatin combined with cyclophosphamide and rituximab (PCR) induced strong responses and was well-tolerated in previously untreated patients with advanced-stage, indolent non-Hodgkin lymphoma (iNHL). After a median patient follow-up of more than 108 months, we performed an intent-to-treat analysis of our 83 participants. Progression-free survival (PFS) rates at 108 months for follicular lymphoma (FL), marginal zone lymphoma (MZL) and small lymphocytic lymphoma (SLL) were 71%, 67% and 15%, respectively, and were affected by clinicopathological characteristics. Ten-year PFS rates for those with beta-2-microglobulin levels <2·2 and ≥2·2 mg/l prior to treatment were 71% and 21%, respectively. Patients without bone marrow involvement had 10-year PFS rates of 72% vs. 29% for those with involvement. At time of analysis, the median overall survival (OS) had not been reached. The OS rate was 64% at 10 years and differed significantly based on histology: 94% for FL, 66% for MZL and 39% for SLL. Long-term toxicities included 18 (21·7%) patients with second malignancies and 2 (2·4%) who developed myelodysplastic syndrome after receiving additional lines of chemotherapy. Our 10-year follow-up analysis confirms that PCR is an effective, robust and tolerable treatment regimen for patients with iNHL. ### Response: cyclophosphamide, rituximab, pentostatin

70e681adca9791cf2e10d9bd14f4c430

Once-weekly isoniazid and rifapentine for 3 months is a treatment option in persons with human immunodeficiency virus and latent tuberculosis infection .

Cytokine-Mediated Systemic Adverse Drug Reactions in a Drug-Drug Interaction Study of Dolutegravir With Once-Weekly Isoniazid and Rifapentine. Once-weekly isoniazid and rifapentine for 3 months is a treatment option in persons with human immunodeficiency virus and latent tuberculosis infection . This study aimed to examine pharmacokinetic drug-drug interactions between this regimen and dolutegravir, a first-line antiretroviral medication. ### methods This was a single-center, open-label, fixed-sequence, drug-drug interaction study in healthy volunteers. Subjects received oral dolutegravir 50 mg once daily alone (days 1-4) and concomitantly with once-weekly isoniazid 900 mg, rifapentine 900 mg, and pyridoxine 50 mg (days 5-19). dolutegravir concentrations were measured on days 4, 14, and 19, and rifapentine, 25-desacetyl-rifapentine, and isoniazid concentrations were measured on day 19. Cytokines and antidrug antibodies to isoniazid and rifapentine were examined at select time points. ### results The study was terminated following the development of flu-like syndrome and elevated aminotransferase levels in 2 of 4 subjects after the third isoniazid-rifapentine dose. Markedly elevated levels of interferon-γ, CXCL10, C-reactive protein, and other cytokines were temporally associated with symptoms. Antidrug antibodies were infrequently detected. dolutegravir area under the curve (AUC) was decreased by 46% (90% confidence interval, 27-110%; P = .13) on day 14. rifapentine and 25-desacetyl rifapentine levels on day 19 were comparable to reference data, whereas isoniazid AUCs were approximately 67%-92% higher in the subjects who developed toxicities. ### conclusions The combined use of dolutegravir with once-weekly isoniazid-rifapentine resulted in unexpected and serious toxicities that were mediated by endogenous cytokine release. Additional investigations are necessary to examine the safety and efficacy of coadministering these medications. ### Clinical Trials Registration NCT02771249.

https://pubmed.ncbi.nlm.nih.gov/29415190/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Cytokine-Mediated Systemic Adverse Drug Reactions in a Drug-Drug Interaction Study of Dolutegravir With Once-Weekly Isoniazid and Rifapentine. Once-weekly isoniazid and rifapentine for 3 months is a treatment option in persons with human immunodeficiency virus and latent tuberculosis infection . This study aimed to examine pharmacokinetic drug-drug interactions between this regimen and dolutegravir, a first-line antiretroviral medication. ### methods This was a single-center, open-label, fixed-sequence, drug-drug interaction study in healthy volunteers. Subjects received oral dolutegravir 50 mg once daily alone (days 1-4) and concomitantly with once-weekly isoniazid 900 mg, rifapentine 900 mg, and pyridoxine 50 mg (days 5-19). dolutegravir concentrations were measured on days 4, 14, and 19, and rifapentine, 25-desacetyl-rifapentine, and isoniazid concentrations were measured on day 19. Cytokines and antidrug antibodies to isoniazid and rifapentine were examined at select time points. ### results The study was terminated following the development of flu-like syndrome and elevated aminotransferase levels in 2 of 4 subjects after the third isoniazid-rifapentine dose. Markedly elevated levels of interferon-γ, CXCL10, C-reactive protein, and other cytokines were temporally associated with symptoms. Antidrug antibodies were infrequently detected. dolutegravir area under the curve (AUC) was decreased by 46% (90% confidence interval, 27-110%; P = .13) on day 14. rifapentine and 25-desacetyl rifapentine levels on day 19 were comparable to reference data, whereas isoniazid AUCs were approximately 67%-92% higher in the subjects who developed toxicities. ### conclusions The combined use of dolutegravir with once-weekly isoniazid-rifapentine resulted in unexpected and serious toxicities that were mediated by endogenous cytokine release. Additional investigations are necessary to examine the safety and efficacy of coadministering these medications. ### Clinical Trials Registration NCT02771249. ### Response: isoniazid, rifapentine

5e01b68299caff14016a31896c325af2

We investigated the effects of these inhibitors on other anticancer drugs including docetaxel , vinblastine , doxorubicin , 10-Hydroxycamptothecin ( 10-HCPT ) and cisplatin and find that both inhibitors induces DU145-TxR cells to be more sensitive only to the microtubule-targeting drugs ( paclitaxel , docetaxel and vinblastine ) .

The Upregulation of PI3K/Akt and MAP Kinase Pathways is Associated with Resistance of Microtubule-Targeting Drugs in Prostate Cancer. Resistance is a significant limitation to the effectiveness of cancer therapies. The PI3K/Akt and MAP kinase pathways play important roles in a variety of normal cellular processes and tumorigenesis. This study is designed to explore the relationship of these signaling pathways with multidrug resistance in prostate cancer (PCa). The PI3K/Akt and MAP kinase pathways were investigated utilizing paclitaxel resistant DU145-TxR PCa cells and their parental non-resistant DU145 cells to determine their relationship with resistance to paclitaxel and other anticancer drugs. Our results demonstrate that the PI3K/Akt and MAP kinase pathways are upregulated in DU145-TxR cells compared to the DU145 cells. Inactivating these pathways using the PI3K/Akt pathway inhibitor LY294002 or the MAP kinase pathway inhibitor PD98059 renders the DU145-TxR cells more sensitive to paclitaxel. We investigated the effects of these inhibitors on other anticancer drugs including docetaxel , vinblastine , doxorubicin , 10-Hydroxycamptothecin ( 10-HCPT ) and cisplatin and find that both inhibitors induces DU145-TxR cells to be more sensitive only to the microtubule-targeting drugs ( paclitaxel , docetaxel and vinblastine ) . Furthermore, the treatment with these inhibitors induces cleaved-PARP production in DU145-TxR cells, suggesting that apoptosis induction might be one of the mechanisms for the reversal of drug resistance. In conclusion, the PI3K/Akt and MAP kinase pathways are associated with resistance to multiple chemotherapeutic drugs. Inactivating these pathways renders these PCa cells more sensitive to microtubule-targeting drugs such as paclitaxel, docetaxel and vinblastine. Combination therapies with novel inhibitors of these two signaling pathways potentially represents a more effective treatment for drug resistant PCa.

https://pubmed.ncbi.nlm.nih.gov/25640606/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: The Upregulation of PI3K/Akt and MAP Kinase Pathways is Associated with Resistance of Microtubule-Targeting Drugs in Prostate Cancer. Resistance is a significant limitation to the effectiveness of cancer therapies. The PI3K/Akt and MAP kinase pathways play important roles in a variety of normal cellular processes and tumorigenesis. This study is designed to explore the relationship of these signaling pathways with multidrug resistance in prostate cancer (PCa). The PI3K/Akt and MAP kinase pathways were investigated utilizing paclitaxel resistant DU145-TxR PCa cells and their parental non-resistant DU145 cells to determine their relationship with resistance to paclitaxel and other anticancer drugs. Our results demonstrate that the PI3K/Akt and MAP kinase pathways are upregulated in DU145-TxR cells compared to the DU145 cells. Inactivating these pathways using the PI3K/Akt pathway inhibitor LY294002 or the MAP kinase pathway inhibitor PD98059 renders the DU145-TxR cells more sensitive to paclitaxel. We investigated the effects of these inhibitors on other anticancer drugs including docetaxel , vinblastine , doxorubicin , 10-Hydroxycamptothecin ( 10-HCPT ) and cisplatin and find that both inhibitors induces DU145-TxR cells to be more sensitive only to the microtubule-targeting drugs ( paclitaxel , docetaxel and vinblastine ) . Furthermore, the treatment with these inhibitors induces cleaved-PARP production in DU145-TxR cells, suggesting that apoptosis induction might be one of the mechanisms for the reversal of drug resistance. In conclusion, the PI3K/Akt and MAP kinase pathways are associated with resistance to multiple chemotherapeutic drugs. Inactivating these pathways renders these PCa cells more sensitive to microtubule-targeting drugs such as paclitaxel, docetaxel and vinblastine. Combination therapies with novel inhibitors of these two signaling pathways potentially represents a more effective treatment for drug resistant PCa. ### Response: docetaxel, vinblastine, doxorubicin, cisplatin, paclitaxel, docetaxel, vinblastine

960105c5f66a50001d208fdbe4f96ccb

Group B : From January , 1976 to December , 1980 , 55 evaluable patients participated in a consecutive study that added Adriamycin ( doxorubicin ) and cyclophosphamide to the former induction regimen .

Comparison of two consecutive trials for treatment of childhood non-Hodgkin's lymphoma. Two consecutive trials for the treatment of childhood non-Hodgkin's lymphoma were evaluated, carried out by the same cooperative groups. Group A: From June, 1973 to December, 1975, 50 evaluable patients under 16 years of age participated in a study that included vincristine and prednisone plus surgery and/or radiotherapy as induction. This was followed by 2400 rad of cranial radiotherapy plus 5 doses of intrathecal methotrexate-dexamethasone and anti-leukemia (6-mercaptopurine, methotrexate, cyclophosphamide) or anti-lymphoma (cyclophosphamide, vincristine, procarbazine, and prednisone) maintenance treatment. Group B : From January , 1976 to December , 1980 , 55 evaluable patients participated in a consecutive study that added Adriamycin ( doxorubicin ) and cyclophosphamide to the former induction regimen . Central nervous system (CNS) prevention was performed with 5 doses of intrathecal methotrexate-dexamethasone. Maintenance treatment was the same. Prognostic factors as stage and primary site were comparable in both groups. A total of 33 (66%) of 50 children of Group A and 48 (87%) of 55 children of Group B achieved complete remission (P less than 0.005). Disease-free survival at 60 months was 27% in Group A and 49% in Group B; for Stage I-II, 30% in Group A and 85% in Group B (P less than 0.025); for Stage III-IV 28% in Group A and 36% in Group B (not significant). In Group A, 9.1% and in Group B, 8.3% had primary CNS relapse. Both maintenance schedules had the same relapse rate. It was concluded that: (1) the addition of Adriamycin and cyclophosphamide to vincristine-prednisone in Group B produces a higher rate of complete remission in Stage III-IV, a higher rate of disease-free survival in Stage I-II, and a higher survival rate in all stages; (2) CNS prevention with intrathecal methotrexate-dexamethasone is equally effective as cranial radiation plus intrathecal methotrexate-dexamethasone; and (3) anti-leukemia and anti-lymphoma maintenance are equally effective in the context of this study.

https://pubmed.ncbi.nlm.nih.gov/6388820/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Comparison of two consecutive trials for treatment of childhood non-Hodgkin's lymphoma. Two consecutive trials for the treatment of childhood non-Hodgkin's lymphoma were evaluated, carried out by the same cooperative groups. Group A: From June, 1973 to December, 1975, 50 evaluable patients under 16 years of age participated in a study that included vincristine and prednisone plus surgery and/or radiotherapy as induction. This was followed by 2400 rad of cranial radiotherapy plus 5 doses of intrathecal methotrexate-dexamethasone and anti-leukemia (6-mercaptopurine, methotrexate, cyclophosphamide) or anti-lymphoma (cyclophosphamide, vincristine, procarbazine, and prednisone) maintenance treatment. Group B : From January , 1976 to December , 1980 , 55 evaluable patients participated in a consecutive study that added Adriamycin ( doxorubicin ) and cyclophosphamide to the former induction regimen . Central nervous system (CNS) prevention was performed with 5 doses of intrathecal methotrexate-dexamethasone. Maintenance treatment was the same. Prognostic factors as stage and primary site were comparable in both groups. A total of 33 (66%) of 50 children of Group A and 48 (87%) of 55 children of Group B achieved complete remission (P less than 0.005). Disease-free survival at 60 months was 27% in Group A and 49% in Group B; for Stage I-II, 30% in Group A and 85% in Group B (P less than 0.025); for Stage III-IV 28% in Group A and 36% in Group B (not significant). In Group A, 9.1% and in Group B, 8.3% had primary CNS relapse. Both maintenance schedules had the same relapse rate. It was concluded that: (1) the addition of Adriamycin and cyclophosphamide to vincristine-prednisone in Group B produces a higher rate of complete remission in Stage III-IV, a higher rate of disease-free survival in Stage I-II, and a higher survival rate in all stages; (2) CNS prevention with intrathecal methotrexate-dexamethasone is equally effective as cranial radiation plus intrathecal methotrexate-dexamethasone; and (3) anti-leukemia and anti-lymphoma maintenance are equally effective in the context of this study. ### Response: doxorubicin, cyclophosphamide

db3dec1a94dc53bf5435039c482e060c

When given in repeated doses from 6 h on , 50 g followed by 12.5 g at 6-h intervals , charcoal shortened the serum half-life of amitriptyline by 20 % and that of nortriptyline by 35 % ( p less than 0.05 ) .

Pharmacokinetics of amitriptyline influenced by oral charcoal and urine pH. The effects of orally given activated charcoal, sodium bicarbonate and ammonium chloride on the pharmacokinetics of amitriptyline were studied in 6 volunteers in a randomized, cross-over study. The serum and urine concentrations of amitriptyline and nortriptyline were determined by HPLC for up to 72 h. activated charcoal (50 g), given within 5 min of the amitriptyline hydrochloride dose (75 mg), reduced its absorption by 99%. When given in repeated doses from 6 h on , 50 g followed by 12.5 g at 6-h intervals , charcoal shortened the serum half-life of amitriptyline by 20 % and that of nortriptyline by 35 % ( p less than 0.05 ) . The renal excretions of amitriptyline and nortriptyline increased 1000-fold by the acidification of urine pH to 4. However, the cumulative excretion of amitriptyline and nortriptyline even into acidic urine only accounted for up to 5% of the dose during 72 h. Since urinary pH has a great influence on the ratio of urinary versus serum amitriptyline and nortriptyline concentrations, pH should be taken into consideration, when the clinical significance of their concentrations in urine is evaluated. activated charcoal in adequate doses very effectively prevents the absorption of that fraction of amitriptyline which is in the stomach at the time of charcoal administration. Furthermore, given in repeated oral doses, charcoal increases, to some extent, the rate of elimination of amitriptyline and nortriptyline, probably by interrupting their enterohepatic or enteroenteric circulation.

https://pubmed.ncbi.nlm.nih.gov/3015809/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Pharmacokinetics of amitriptyline influenced by oral charcoal and urine pH. The effects of orally given activated charcoal, sodium bicarbonate and ammonium chloride on the pharmacokinetics of amitriptyline were studied in 6 volunteers in a randomized, cross-over study. The serum and urine concentrations of amitriptyline and nortriptyline were determined by HPLC for up to 72 h. activated charcoal (50 g), given within 5 min of the amitriptyline hydrochloride dose (75 mg), reduced its absorption by 99%. When given in repeated doses from 6 h on , 50 g followed by 12.5 g at 6-h intervals , charcoal shortened the serum half-life of amitriptyline by 20 % and that of nortriptyline by 35 % ( p less than 0.05 ) . The renal excretions of amitriptyline and nortriptyline increased 1000-fold by the acidification of urine pH to 4. However, the cumulative excretion of amitriptyline and nortriptyline even into acidic urine only accounted for up to 5% of the dose during 72 h. Since urinary pH has a great influence on the ratio of urinary versus serum amitriptyline and nortriptyline concentrations, pH should be taken into consideration, when the clinical significance of their concentrations in urine is evaluated. activated charcoal in adequate doses very effectively prevents the absorption of that fraction of amitriptyline which is in the stomach at the time of charcoal administration. Furthermore, given in repeated oral doses, charcoal increases, to some extent, the rate of elimination of amitriptyline and nortriptyline, probably by interrupting their enterohepatic or enteroenteric circulation. ### Response: amitriptyline, nortriptyline

db0e74273491043a8d918e7ddae08e7d

The median overall survival time was 22.7 months in the docetaxel arm and 22.4 months in the paclitaxel arm .

A phase II randomized study of two taxanes and cisplatin for metastatic breast cancer after anthracycline: a final analysis. The purpose of the study is to compare two taxanes/cisplatin combinations for metastatic breast cancer in terms of time to disease progression, response rates and toxicity. ### methods Between April 2000 and December 2002, 101 patients with advanced breast carcinoma, previously treated with an anthracycline but not with a taxane, were enrolled. Fifty patients were treated with docetaxel 60 mg/m2 and cisplatin 50 mg/m2, and 51 patients were treated with paclitaxel 175 mg/m2 and cisplatin 50 mg/m2. Each cycle repeated every 3 weeks. ### results The overall response rate was 62.5 and 42.6% in the docetaxel and palcitaxel groups respectively (P = 0.06). Median time to disease progression was 9.8 and 6.5 months in docetaxel and paclitaxel groups respectively (P = 0.15). The median overall survival time was 22.7 months in the docetaxel arm and 22.4 months in the paclitaxel arm . Grade 3/4 arthralgia/myalgia, sensory neuropathy and anemia occurred more frequently in the paclitaxel arm, while more mucositis, fatigue and neutropenia occurred in the docetaxel arm. ### conclusion Taxane/cisplatin combinations were active for advanced breast cancer, while there appeared to be evidence in favor of a docetaxel/cisplatin combination. The toxicity in favor of docetaxel/cisplatin warrants future first-line clinical trials.

https://pubmed.ncbi.nlm.nih.gov/17172351/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: A phase II randomized study of two taxanes and cisplatin for metastatic breast cancer after anthracycline: a final analysis. The purpose of the study is to compare two taxanes/cisplatin combinations for metastatic breast cancer in terms of time to disease progression, response rates and toxicity. ### methods Between April 2000 and December 2002, 101 patients with advanced breast carcinoma, previously treated with an anthracycline but not with a taxane, were enrolled. Fifty patients were treated with docetaxel 60 mg/m2 and cisplatin 50 mg/m2, and 51 patients were treated with paclitaxel 175 mg/m2 and cisplatin 50 mg/m2. Each cycle repeated every 3 weeks. ### results The overall response rate was 62.5 and 42.6% in the docetaxel and palcitaxel groups respectively (P = 0.06). Median time to disease progression was 9.8 and 6.5 months in docetaxel and paclitaxel groups respectively (P = 0.15). The median overall survival time was 22.7 months in the docetaxel arm and 22.4 months in the paclitaxel arm . Grade 3/4 arthralgia/myalgia, sensory neuropathy and anemia occurred more frequently in the paclitaxel arm, while more mucositis, fatigue and neutropenia occurred in the docetaxel arm. ### conclusion Taxane/cisplatin combinations were active for advanced breast cancer, while there appeared to be evidence in favor of a docetaxel/cisplatin combination. The toxicity in favor of docetaxel/cisplatin warrants future first-line clinical trials. ### Response: docetaxel, paclitaxel

faf0c9f77be3f3da48e14be921b759f0

We hypothesized that Aurora A kinase ( AK ) contributes to castrate resistance in prostate cancer ( PCa ) and that inhibiting AK with alisertib can resensitize PCa cells to androgen receptor ( AR ) inhibitor abiraterone .

A Phase I/II Study of the Investigational Drug Alisertib in Combination With Abiraterone and Prednisone for Patients With Metastatic Castration-Resistant Prostate Cancer Progressing on Abiraterone. Patients with metastatic castration-resistant prostate cancer did not tolerate the combination of alisertib with abiraterone and prednisone.There was no clear signal indicating that adding alisertib might be beneficial for those patients progressing on abiraterone. ### background We hypothesized that Aurora A kinase ( AK ) contributes to castrate resistance in prostate cancer ( PCa ) and that inhibiting AK with alisertib can resensitize PCa cells to androgen receptor ( AR ) inhibitor abiraterone . ### methods This was a phase I/II trial to determine the safety and efficacy of alisertib when given in combination with abiraterone plus prednisone (AP). Metastatic castration-resistant prostate cancer (mCRPC) patients were treated with dose escalation (alisertib at 30, 40, and 50 mg orally b.i.d., days 1-7 every 21 days) per standard 3+3 design. ### results Nine of 43 planned subjects were enrolled. The maximum tolerated dose (MTD) was not reached, and the dose-limiting toxicities (DLTs) included neutropenic fever (1 of 9), neutropenia (1 of 9), fatigue with memory impairment (1 of 9), and diarrhea/mucositis (1 of 9). No prostate-specific antigen (PSA) decrease or circulating tumor cell (CTC) changes were observed during the study. Pharmacodynamically, adding alisertib did not affect total testosterone or dehydroepiandrosterone (DHEA) levels. There was some change in neuroendocrine markers after therapy. Mean duration on study was 2.5 months. The trial was terminated early. ### conclusion A tolerable dose of alisertib in combination with AP in mCRPC was not established in this study. There was no clear signal indicating that alisertib might be beneficial for patients with mCRPC progressing on abiraterone.

https://pubmed.ncbi.nlm.nih.gov/28178640/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: A Phase I/II Study of the Investigational Drug Alisertib in Combination With Abiraterone and Prednisone for Patients With Metastatic Castration-Resistant Prostate Cancer Progressing on Abiraterone. Patients with metastatic castration-resistant prostate cancer did not tolerate the combination of alisertib with abiraterone and prednisone.There was no clear signal indicating that adding alisertib might be beneficial for those patients progressing on abiraterone. ### background We hypothesized that Aurora A kinase ( AK ) contributes to castrate resistance in prostate cancer ( PCa ) and that inhibiting AK with alisertib can resensitize PCa cells to androgen receptor ( AR ) inhibitor abiraterone . ### methods This was a phase I/II trial to determine the safety and efficacy of alisertib when given in combination with abiraterone plus prednisone (AP). Metastatic castration-resistant prostate cancer (mCRPC) patients were treated with dose escalation (alisertib at 30, 40, and 50 mg orally b.i.d., days 1-7 every 21 days) per standard 3+3 design. ### results Nine of 43 planned subjects were enrolled. The maximum tolerated dose (MTD) was not reached, and the dose-limiting toxicities (DLTs) included neutropenic fever (1 of 9), neutropenia (1 of 9), fatigue with memory impairment (1 of 9), and diarrhea/mucositis (1 of 9). No prostate-specific antigen (PSA) decrease or circulating tumor cell (CTC) changes were observed during the study. Pharmacodynamically, adding alisertib did not affect total testosterone or dehydroepiandrosterone (DHEA) levels. There was some change in neuroendocrine markers after therapy. Mean duration on study was 2.5 months. The trial was terminated early. ### conclusion A tolerable dose of alisertib in combination with AP in mCRPC was not established in this study. There was no clear signal indicating that alisertib might be beneficial for patients with mCRPC progressing on abiraterone. ### Response: alisertib, abiraterone

64be1cf1b7842c1f1e561a1885ffcb34

Tanespimycin plus trastuzumab is well tolerated and has antitumor activity in patients with HER-2 + breast cancer whose tumors have progressed during treatment with trastuzumab .

Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a phase I dose-escalation study. This phase I study examined whether a heat shock protein (Hsp) 90 inhibitor tanespimycin (17-AAG; KOS-953) could be administered safely in combination with trastuzumab at a dose that inhibits Hsp90 function in vivo in lymphocytes. ### Patients And Methods Patients with an advanced solid tumor progressing during standard therapy were eligible. Patients were treated with weekly trastuzumab followed by intravenous tanespimycin, assessed in escalating dose levels. ### results Twenty-five patients were enrolled onto four tanespimycin dose levels: 225 (n = 4), 300 (n = 3), 375 (n = 8), and 450 mg/m2 (n = 10). Dose-limiting toxicity (DLT) was observed at the third and fourth cohort (1 patient each): more than 2-week delay for grade 4 fatigue/grade 2 nausea and anorexia (375 mg/m2); more than 2-week delay for thrombocytopenia (450 mg/m2). Drug-related grade 3 toxicity included emesis, increased ALT, hypersensitivity reactions (two patients each), and drug-induced thrombocytopenia (n = 1). Common mild to moderate toxicities included fatigue, nausea, diarrhea, emesis, headache, rash/pruritus, increased AST/ALT, and anorexia. Pharmacokinetic analysis demonstrated no difference in tanespimycin kinetics with or without trastuzumab. Pharmacodynamic testing showed reactive induction of Hsp70 (a marker of Hsp90 inhibition) in lymphocytes at all dose levels. Antitumor activity was noted (partial response, n = 1; minor response, n = 4; stable disease > or = 4 months, n = 4). Tumor regressions were seen only in patients with human epidermal growth factor receptor 2 (HER-2)-positive metastatic breast cancer. ### conclusion Tanespimycin plus trastuzumab is well tolerated and has antitumor activity in patients with HER-2 + breast cancer whose tumors have progressed during treatment with trastuzumab . These data suggest that Hsp90 function can be inhibited in vivo to a degree sufficient to cause inhibition of tumor growth.

https://pubmed.ncbi.nlm.nih.gov/18048823/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a phase I dose-escalation study. This phase I study examined whether a heat shock protein (Hsp) 90 inhibitor tanespimycin (17-AAG; KOS-953) could be administered safely in combination with trastuzumab at a dose that inhibits Hsp90 function in vivo in lymphocytes. ### Patients And Methods Patients with an advanced solid tumor progressing during standard therapy were eligible. Patients were treated with weekly trastuzumab followed by intravenous tanespimycin, assessed in escalating dose levels. ### results Twenty-five patients were enrolled onto four tanespimycin dose levels: 225 (n = 4), 300 (n = 3), 375 (n = 8), and 450 mg/m2 (n = 10). Dose-limiting toxicity (DLT) was observed at the third and fourth cohort (1 patient each): more than 2-week delay for grade 4 fatigue/grade 2 nausea and anorexia (375 mg/m2); more than 2-week delay for thrombocytopenia (450 mg/m2). Drug-related grade 3 toxicity included emesis, increased ALT, hypersensitivity reactions (two patients each), and drug-induced thrombocytopenia (n = 1). Common mild to moderate toxicities included fatigue, nausea, diarrhea, emesis, headache, rash/pruritus, increased AST/ALT, and anorexia. Pharmacokinetic analysis demonstrated no difference in tanespimycin kinetics with or without trastuzumab. Pharmacodynamic testing showed reactive induction of Hsp70 (a marker of Hsp90 inhibition) in lymphocytes at all dose levels. Antitumor activity was noted (partial response, n = 1; minor response, n = 4; stable disease > or = 4 months, n = 4). Tumor regressions were seen only in patients with human epidermal growth factor receptor 2 (HER-2)-positive metastatic breast cancer. ### conclusion Tanespimycin plus trastuzumab is well tolerated and has antitumor activity in patients with HER-2 + breast cancer whose tumors have progressed during treatment with trastuzumab . These data suggest that Hsp90 function can be inhibited in vivo to a degree sufficient to cause inhibition of tumor growth. ### Response: Tanespimycin, trastuzumab, trastuzumab

259fcb11e8020d04ee63f8e43cb90c7a

It contains data on prophylaxis with mefloquine ( n = 48,264 ) , with chloroquine ( 6,752 ) , with chloroquine plus proguanil ( 19,727 ) , and with no prophylaxis ( 3,871 ) .

Tolerability and Effectiveness of Malaria Chemoprophylaxis with Mefloquine or Chloroquine with or without Co-medication. Background: To determine the relevance of drug interactions with co-medication for effectiveness and tolerability of antimalarial chemoprophylaxis. Method: A database (MALPRO2) on travelers on their flight home from Africa to Europe between July 1988 and December 1991 was reanalyzed. It contains data on prophylaxis with mefloquine ( n = 48,264 ) , with chloroquine ( 6,752 ) , with chloroquine plus proguanil ( 19,727 ) , and with no prophylaxis ( 3,871 ) . The comparison of rates of malaria incidence and adverse events (AEs) between users and nonusers of co-medication was expressed by relative risk (RR). Results: Fifty-three percent of travelers (63% of females, 43% of males) used co-medication in all prophylaxis groups, with an average of 1.35 additional drugs per person and about two AEs reported per person. With the exception of antidiarrheals plus mefloquine, malaria incidence with co-medication was lower (RR = 0.8) than without co-medication. In all regimens, the proportion of travelers reporting AEs was about 1.5-fold with co-medication (p<.01); that reporting severe AEs was twice as high as compared to with no co-medication. mefloquine AE rates for various classes of co-medication were similar to that of chloroquine, with highest AE and severity rates with neuropsychiatric drugs (excluding antiepileptics, RR = 1.9 and 2.9), and lowest rates with cardiovasculars (RR = 1.1 and 1.0). Various co-medications were used with different frequencies in males and females, and the latter reported more AEs. Conclusion: These data suggest that co-medications commonly used by travelers have no significant clinical impact on safety and effectiveness of prophylaxis with mefloquine or chloroquine. Increased frequency and severity of AEs when using co-medication rather is explained by underlying illness.

https://pubmed.ncbi.nlm.nih.gov/9815496/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Tolerability and Effectiveness of Malaria Chemoprophylaxis with Mefloquine or Chloroquine with or without Co-medication. Background: To determine the relevance of drug interactions with co-medication for effectiveness and tolerability of antimalarial chemoprophylaxis. Method: A database (MALPRO2) on travelers on their flight home from Africa to Europe between July 1988 and December 1991 was reanalyzed. It contains data on prophylaxis with mefloquine ( n = 48,264 ) , with chloroquine ( 6,752 ) , with chloroquine plus proguanil ( 19,727 ) , and with no prophylaxis ( 3,871 ) . The comparison of rates of malaria incidence and adverse events (AEs) between users and nonusers of co-medication was expressed by relative risk (RR). Results: Fifty-three percent of travelers (63% of females, 43% of males) used co-medication in all prophylaxis groups, with an average of 1.35 additional drugs per person and about two AEs reported per person. With the exception of antidiarrheals plus mefloquine, malaria incidence with co-medication was lower (RR = 0.8) than without co-medication. In all regimens, the proportion of travelers reporting AEs was about 1.5-fold with co-medication (p<.01); that reporting severe AEs was twice as high as compared to with no co-medication. mefloquine AE rates for various classes of co-medication were similar to that of chloroquine, with highest AE and severity rates with neuropsychiatric drugs (excluding antiepileptics, RR = 1.9 and 2.9), and lowest rates with cardiovasculars (RR = 1.1 and 1.0). Various co-medications were used with different frequencies in males and females, and the latter reported more AEs. Conclusion: These data suggest that co-medications commonly used by travelers have no significant clinical impact on safety and effectiveness of prophylaxis with mefloquine or chloroquine. Increased frequency and severity of AEs when using co-medication rather is explained by underlying illness. ### Response: mefloquine, chloroquine, chloroquine, proguanil

dd0068d9fba06a8e7c381728dd8e1029

We hypothesized that the brain damage mitigating effect of mild hypothermia after cardiac arrest can be enhanced with thiopental loading , and even more so with the further addition of phenytoin and methylprednisolone .

Thiopental combination treatments for cerebral resuscitation after prolonged cardiac arrest in dogs. Exploratory outcome study. We postulate that mitigating the multifactorial pathogenesis of postischemic encephalopathy requires multifaceted treatments. In preparation for expensive definitive studies, we are reporting here the results of small exploratory series, compared with historic controls with the same model. We hypothesized that the brain damage mitigating effect of mild hypothermia after cardiac arrest can be enhanced with thiopental loading , and even more so with the further addition of phenytoin and methylprednisolone . Twenty-four dogs (four groups of six dogs each) received VF 12.5 min no-flow, reversed with brief cardiopulmonary bypass (CPB), controlled ventilation to 20 h, and intensive care to 96 h. Group 1 with normothermia throughout and randomized group 2 with mild hypothermia (from reperfusion to 2 h) were controls. Then, group 3 received in addition, thiopental 90 mg/kg i.v. over the first 6 h. Then, group 4 received, in addition to group 2 treatment, thiopental 30 mg/kg i.v. over the first 90 min (because the larger dose had produced cardiopulmonary complications), plus phenytoin 15 mg/kg i.v. at 15 min after reperfusion, and methylprednisolone 130 mg/kg i.v. over 20 h. All dogs survived. Best overall performance categories (OPC) achieved (OPC 1 = normal, OPC 5 = brain death) were better in group 2 than group 1 (< 0.05) and numerically better in groups 3 or 4 than in groups 1 or 2. Good cerebral outcome (OPC 1 or 2) was achieved by all six dogs only in group 4 (P < 0.05 group 4 vs. 2). Best NDS were 44 +/- 3% in group 1; 20 +/- 14% in group 2 (P = 0.002); 21 +/- 15% in group 3 (NS vs. group 2); and 7 +/- 8% in group 4 (P = 0.08 vs. group 2). Total brain histologic damage scores (HDS) at 96 h were 156 +/- 38 in group 1; 81 +/- 12 in group 2 (P < 0.001 vs. group 1); 53 +/- 25 in group 3 (P = 0.02 vs. group 2); and 48 +/- 5 in group 4 (P = 0.02 vs. group 2). We conclude that after prolonged cardiac arrest, the already established brain damage mitigating effect of mild immediate postarrest hypothermia might be enhanced by thiopental, and perhaps then further enhanced by adding phenytoin and methylprednisolone.

https://pubmed.ncbi.nlm.nih.gov/10950320/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Thiopental combination treatments for cerebral resuscitation after prolonged cardiac arrest in dogs. Exploratory outcome study. We postulate that mitigating the multifactorial pathogenesis of postischemic encephalopathy requires multifaceted treatments. In preparation for expensive definitive studies, we are reporting here the results of small exploratory series, compared with historic controls with the same model. We hypothesized that the brain damage mitigating effect of mild hypothermia after cardiac arrest can be enhanced with thiopental loading , and even more so with the further addition of phenytoin and methylprednisolone . Twenty-four dogs (four groups of six dogs each) received VF 12.5 min no-flow, reversed with brief cardiopulmonary bypass (CPB), controlled ventilation to 20 h, and intensive care to 96 h. Group 1 with normothermia throughout and randomized group 2 with mild hypothermia (from reperfusion to 2 h) were controls. Then, group 3 received in addition, thiopental 90 mg/kg i.v. over the first 6 h. Then, group 4 received, in addition to group 2 treatment, thiopental 30 mg/kg i.v. over the first 90 min (because the larger dose had produced cardiopulmonary complications), plus phenytoin 15 mg/kg i.v. at 15 min after reperfusion, and methylprednisolone 130 mg/kg i.v. over 20 h. All dogs survived. Best overall performance categories (OPC) achieved (OPC 1 = normal, OPC 5 = brain death) were better in group 2 than group 1 (< 0.05) and numerically better in groups 3 or 4 than in groups 1 or 2. Good cerebral outcome (OPC 1 or 2) was achieved by all six dogs only in group 4 (P < 0.05 group 4 vs. 2). Best NDS were 44 +/- 3% in group 1; 20 +/- 14% in group 2 (P = 0.002); 21 +/- 15% in group 3 (NS vs. group 2); and 7 +/- 8% in group 4 (P = 0.08 vs. group 2). Total brain histologic damage scores (HDS) at 96 h were 156 +/- 38 in group 1; 81 +/- 12 in group 2 (P < 0.001 vs. group 1); 53 +/- 25 in group 3 (P = 0.02 vs. group 2); and 48 +/- 5 in group 4 (P = 0.02 vs. group 2). We conclude that after prolonged cardiac arrest, the already established brain damage mitigating effect of mild immediate postarrest hypothermia might be enhanced by thiopental, and perhaps then further enhanced by adding phenytoin and methylprednisolone. ### Response: phenytoin, methylprednisolone

138ed4d659b783b0815a4433b59d0cff

Caspase-independent mechanisms , mainly based on increased oxidative stress , result from 2-methoxyestradiol , Artesunate , ascorbic acid , Dihydroartemisinin , Evodiamine , b-AP15 , VLX1570 , Erw-ASNase , and TAK-242 .

Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma. Multiple myeloma (MM) remains an incurable tumor due to the high rate of relapse that still occurs. Acquired drug resistance represents the most challenging obstacle to the extension of survival and several studies have been conducted to understand the mechanisms of this phenomenon. Mitochondrial pathways have been extensively investigated, demonstrating that cancer cells become resistant to drugs by reprogramming their metabolic assessment. MM cells acquire resistance to proteasome inhibitors (PIs), activating protection programs, such as a reduction in oxidative stress, down-regulating pro-apoptotic, and up-regulating anti-apoptotic signals. Knowledge of the mechanisms through which tumor cells escape control of the immune system and acquire resistance to drugs has led to the creation of new compounds that can restore the response by leading to cell death. In this scenario, based on all literature data available, our review represents the first collection of anti-mitochondrial compounds able to overcome drug resistance in MM. Caspase-independent mechanisms , mainly based on increased oxidative stress , result from 2-methoxyestradiol , Artesunate , ascorbic acid , Dihydroartemisinin , Evodiamine , b-AP15 , VLX1570 , Erw-ASNase , and TAK-242 . Other agents restore PIs' efficacy through caspase-dependent tools, such as CDDO-Im, NOXA-inhibitors, FTY720, GCS-100, LBH589, a derivative of ellipticine, AT-101, KD5170, SMAC-mimetics, glutaminase-1 (GLS1)-inhibitors, and thenoyltrifluoroacetone. Each of these substances improved the efficacy rates when employed in combination with the most frequently used antimyeloma drugs.

https://pubmed.ncbi.nlm.nih.gov/33669515/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma. Multiple myeloma (MM) remains an incurable tumor due to the high rate of relapse that still occurs. Acquired drug resistance represents the most challenging obstacle to the extension of survival and several studies have been conducted to understand the mechanisms of this phenomenon. Mitochondrial pathways have been extensively investigated, demonstrating that cancer cells become resistant to drugs by reprogramming their metabolic assessment. MM cells acquire resistance to proteasome inhibitors (PIs), activating protection programs, such as a reduction in oxidative stress, down-regulating pro-apoptotic, and up-regulating anti-apoptotic signals. Knowledge of the mechanisms through which tumor cells escape control of the immune system and acquire resistance to drugs has led to the creation of new compounds that can restore the response by leading to cell death. In this scenario, based on all literature data available, our review represents the first collection of anti-mitochondrial compounds able to overcome drug resistance in MM. Caspase-independent mechanisms , mainly based on increased oxidative stress , result from 2-methoxyestradiol , Artesunate , ascorbic acid , Dihydroartemisinin , Evodiamine , b-AP15 , VLX1570 , Erw-ASNase , and TAK-242 . Other agents restore PIs' efficacy through caspase-dependent tools, such as CDDO-Im, NOXA-inhibitors, FTY720, GCS-100, LBH589, a derivative of ellipticine, AT-101, KD5170, SMAC-mimetics, glutaminase-1 (GLS1)-inhibitors, and thenoyltrifluoroacetone. Each of these substances improved the efficacy rates when employed in combination with the most frequently used antimyeloma drugs. ### Response: Artesunate, Dihydroartemisinin

b0d5192b7353b914214db1d91f189d3a

In the xenograft model , more augmented effects were achieved when bortezomib was combined with gemcitabine than gemcitabine alone .

Effects and mechanisms of the combination of suberoylanilide hydroxamic acid and bortezomib on the anticancer property of gemcitabine in pancreatic cancer. Earlier studies that dealt with the combination therapy of gemcitabine and histone deacetylation inhibitors for pancreatic cancer revealed unsatisfactory results. The activation of nuclear factor κB (NF-κB) was referred as one of the attributable causes, and we attempted to overcome this resistance by the addition of a proteasome inhibitor. ### methods The influences of suberoylanilide hydroxamic acid (vorinostat, SAHA), a histone deacetylase inhibitor, and bortezomib, a novel selective antagonist of 26S proteasome, with or without gemcitabine on cell growth and apoptosis and the expressions of related proteins were observed in pancreatic cancer cell lines (MiaPaCa-2 and ASPC-1). The xenograft model of pancreatic cancer was used to notice effects in vivo. ### results vorinostat and bortezomib had independent inhibitory effects and potentiated the antitumor property of gemcitabine in vitro. In the xenograft model , more augmented effects were achieved when bortezomib was combined with gemcitabine than gemcitabine alone . The down-regulation of pAkt and suppression of NF-κB activity was induced by the triple combination. ### conclusions The triple combination of vorinostat, bortezomib, and gemcitabine resulted in the strongest antitumor effects both in vitro and in vivo and pAkt and NF-κB seems to be involved in this process.

https://pubmed.ncbi.nlm.nih.gov/21487323/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Effects and mechanisms of the combination of suberoylanilide hydroxamic acid and bortezomib on the anticancer property of gemcitabine in pancreatic cancer. Earlier studies that dealt with the combination therapy of gemcitabine and histone deacetylation inhibitors for pancreatic cancer revealed unsatisfactory results. The activation of nuclear factor κB (NF-κB) was referred as one of the attributable causes, and we attempted to overcome this resistance by the addition of a proteasome inhibitor. ### methods The influences of suberoylanilide hydroxamic acid (vorinostat, SAHA), a histone deacetylase inhibitor, and bortezomib, a novel selective antagonist of 26S proteasome, with or without gemcitabine on cell growth and apoptosis and the expressions of related proteins were observed in pancreatic cancer cell lines (MiaPaCa-2 and ASPC-1). The xenograft model of pancreatic cancer was used to notice effects in vivo. ### results vorinostat and bortezomib had independent inhibitory effects and potentiated the antitumor property of gemcitabine in vitro. In the xenograft model , more augmented effects were achieved when bortezomib was combined with gemcitabine than gemcitabine alone . The down-regulation of pAkt and suppression of NF-κB activity was induced by the triple combination. ### conclusions The triple combination of vorinostat, bortezomib, and gemcitabine resulted in the strongest antitumor effects both in vitro and in vivo and pAkt and NF-κB seems to be involved in this process. ### Response: bortezomib, gemcitabine, gemcitabine

00d0330eaf9fcbfda83b9dcc6dde58ce

The effectiveness of combination therapy with afatinib and bevacizumab may provide a new therapeutic option for these patients .

Combination therapy with afatinib and bevacizumab in an EGFR-mutated non-small cell lung cancer patient with acquired ERBB2 amplification: A case report. Acquired resistance to reversible EGFR tyrosine kinase inhibitors remains a significant obstacle, and acquired ERBB2 amplification is the most common "bypass" mechanism. For patients with sensitizing EGFR mutation who experience resistance via ERBB2 amplification, no targeted drug has been demonstrated to be effective. ### Patient Concerns A 56-year-old female nonsmoker suffered from left leg paralysis and low back pain. Imaging examination revealed a mass in the anterior segment of the right upper lobe lung and possible multiple metastases in the right hilar, mediastinal lymph nodes, bone metastases, and soft tissue invasion. ### diagnosis Transbronchial lung biopsy revealed a moderately differentiated adenocarcinoma (cT4N2M1c, stage IV). An EGFR exon 19 deletion was identified using amplification refractory mutation system. ### interventions After the patient was treated with gefitinib initiation (250 mg/d) for 15 months, the tumor progressed with ERBB2 amplification revealed by next-generation sequencing test. Then, the patient was started on afatinib (40 mg/d) plus bevacizumab (7.5 mg/kg every 3 weeks). ### outcomes The combination therapy of afatinib and bevacizumab in this patient was effective with some slight side effects. Computed tomography scans showed the tumor shrinkage and the pleural effusion disappeared in the right lung. The overall survival was 23.5 months. ### conclusion To date, there is no targeted therapy approved and demonstrated to be effective for non-small cell lung cancer patients with EGFR sensitizing mutations, and ERBB2 amplification. The effectiveness of combination therapy with afatinib and bevacizumab may provide a new therapeutic option for these patients .

https://pubmed.ncbi.nlm.nih.gov/33663050/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Combination therapy with afatinib and bevacizumab in an EGFR-mutated non-small cell lung cancer patient with acquired ERBB2 amplification: A case report. Acquired resistance to reversible EGFR tyrosine kinase inhibitors remains a significant obstacle, and acquired ERBB2 amplification is the most common "bypass" mechanism. For patients with sensitizing EGFR mutation who experience resistance via ERBB2 amplification, no targeted drug has been demonstrated to be effective. ### Patient Concerns A 56-year-old female nonsmoker suffered from left leg paralysis and low back pain. Imaging examination revealed a mass in the anterior segment of the right upper lobe lung and possible multiple metastases in the right hilar, mediastinal lymph nodes, bone metastases, and soft tissue invasion. ### diagnosis Transbronchial lung biopsy revealed a moderately differentiated adenocarcinoma (cT4N2M1c, stage IV). An EGFR exon 19 deletion was identified using amplification refractory mutation system. ### interventions After the patient was treated with gefitinib initiation (250 mg/d) for 15 months, the tumor progressed with ERBB2 amplification revealed by next-generation sequencing test. Then, the patient was started on afatinib (40 mg/d) plus bevacizumab (7.5 mg/kg every 3 weeks). ### outcomes The combination therapy of afatinib and bevacizumab in this patient was effective with some slight side effects. Computed tomography scans showed the tumor shrinkage and the pleural effusion disappeared in the right lung. The overall survival was 23.5 months. ### conclusion To date, there is no targeted therapy approved and demonstrated to be effective for non-small cell lung cancer patients with EGFR sensitizing mutations, and ERBB2 amplification. The effectiveness of combination therapy with afatinib and bevacizumab may provide a new therapeutic option for these patients . ### Response: afatinib, bevacizumab

af2a75784262b4e7c5c2ad00bb39becb

Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after abiraterone .

Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after abiraterone . The optimal sequencing of the multiple active agents now available for metastatic castration-resistant prostate cancer (mCRPC) is unclear. Prior reports have suggested diminished responses to sequential lines of androgen receptor (AR)-targeted therapies, but it is unknown whether subsequent taxane-based chemotherapy may be more effective than sequential AR-targeting treatment. We sought to evaluate the clinical activity of enzalutamide versus docetaxel in men with mCRPC who progressed on abiraterone. ### methods We performed a single-institution retrospective analysis of consecutive mCRPC patients who had progressed on abiraterone therapy and subsequently received either enzalutamide (n=30) or docetaxel (n=31). We evaluated clinical outcomes including prostate-specific antigen decline of >30% (PSA30) or >50% (PSA50), PSA-progression-free survival (PSA-PFS), and clinical/radiographic PFS. We performed multivariable modeling to control for baseline and on-treatment differences between groups. ### results Compared to subjects who received enzalutamide post-abiraterone, subjects who received docetaxel post-abiraterone had more bone metastases, more visceral metastases, higher baseline PSA, and had more frequent PSA tests while on-treatment. There were no significant differences in PSA30 (41% for enzalutamide vs. 53% for docetaxel) or PSA50 (34% vs. 40%) response rates between the two groups; there remained no difference after stratifying by presence/absence of prior response to abiraterone. Median PSA-PFS was 4.1 versus 4.1 months for the enzalutamide and docetaxel cohorts, respectively (HR 1.35, 95% CI, 0.53-3.66, P=0.502). Median PFS was 4.7 versus 4.4 months, respectively (HR 1.44, 95% CI, 0.77-2.71, P=0.257). PSA-PFS and PFS did not differ after stratifying by prior response to abiraterone. In multivariable analyses, there were no significant differences in PSA-PFS or PFS between the two groups. ### conclusions Treatment with either enzalutamide or docetaxel produced modest PSA responses and PFS intervals in this abiraterone-pretreated mCRPC population. In this retrospective study with small sample size, no significant differences in outcomes were observed between groups. Therefore, either enzalutamide or docetaxel may be a reasonable option in men who have progressed on abiraterone.

https://pubmed.ncbi.nlm.nih.gov/25053178/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after abiraterone . The optimal sequencing of the multiple active agents now available for metastatic castration-resistant prostate cancer (mCRPC) is unclear. Prior reports have suggested diminished responses to sequential lines of androgen receptor (AR)-targeted therapies, but it is unknown whether subsequent taxane-based chemotherapy may be more effective than sequential AR-targeting treatment. We sought to evaluate the clinical activity of enzalutamide versus docetaxel in men with mCRPC who progressed on abiraterone. ### methods We performed a single-institution retrospective analysis of consecutive mCRPC patients who had progressed on abiraterone therapy and subsequently received either enzalutamide (n=30) or docetaxel (n=31). We evaluated clinical outcomes including prostate-specific antigen decline of >30% (PSA30) or >50% (PSA50), PSA-progression-free survival (PSA-PFS), and clinical/radiographic PFS. We performed multivariable modeling to control for baseline and on-treatment differences between groups. ### results Compared to subjects who received enzalutamide post-abiraterone, subjects who received docetaxel post-abiraterone had more bone metastases, more visceral metastases, higher baseline PSA, and had more frequent PSA tests while on-treatment. There were no significant differences in PSA30 (41% for enzalutamide vs. 53% for docetaxel) or PSA50 (34% vs. 40%) response rates between the two groups; there remained no difference after stratifying by presence/absence of prior response to abiraterone. Median PSA-PFS was 4.1 versus 4.1 months for the enzalutamide and docetaxel cohorts, respectively (HR 1.35, 95% CI, 0.53-3.66, P=0.502). Median PFS was 4.7 versus 4.4 months, respectively (HR 1.44, 95% CI, 0.77-2.71, P=0.257). PSA-PFS and PFS did not differ after stratifying by prior response to abiraterone. In multivariable analyses, there were no significant differences in PSA-PFS or PFS between the two groups. ### conclusions Treatment with either enzalutamide or docetaxel produced modest PSA responses and PFS intervals in this abiraterone-pretreated mCRPC population. In this retrospective study with small sample size, no significant differences in outcomes were observed between groups. Therefore, either enzalutamide or docetaxel may be a reasonable option in men who have progressed on abiraterone. ### Response: enzalutamide, docetaxel, abiraterone

864521b20a79cd641bf02b5c5c24716a

The use of cyclophosphamide in patients with NSVN is controversial , but recent retrospective data suggest that those treated with prednisone and cyclophosphamide from the outset fare better than those initially treated only with prednisone .

Therapy for vasculitic neuropathies. The term vasculitis refers to a pathologic condition defined by inflammatory cell infiltration and destruction of blood vessels. Systemic vasculitis is classified as primary (eg, polyarteritis nodosa, Churg-Strauss syndrome) or secondary, the latter associated with connective tissue disorders, infections, medications, and rarely, as a paraneoplastic phenomenon. Neuropathy is a common complication of systemic vasculitis and is related to ischemic nerve fiber damage with axon loss. Peripheral neuropathy may be the sole manifestation of vasculitis, a condition termed nonsystemic vasculitic neuropathy (NSVN). Treatment of vasculitic neuropathy requires long-term immunosuppressive therapies with potential side effects. The diagnosis of vasculitis should be established by tissue (preferably nerve) biopsy. High-dose prednisone is the standard platform therapy for patients with systemic and NSVN; for those with systemic vasculitis, at least 3 to 12 months of treatment with cyclophosphamide (monthly intravenous pulse or daily oral therapy) is also necessary to sustain remission and allow successful prednisone tapering. The use of cyclophosphamide in patients with NSVN is controversial , but recent retrospective data suggest that those treated with prednisone and cyclophosphamide from the outset fare better than those initially treated only with prednisone . If prednisone is administered as monotherapy, cyclophosphamide should be added after several months if there is no improvement or relapse occurs with tapering of prednisone. Intravenous pulse and daily oral cyclophosphamide probably offer similar efficacy, although the risk of complications is greater with oral therapy. azathioprine can be safely substituted for cyclophosphamide after 3 months without an increased relapse rate. azathioprine, methotrexate, intravenous immune globulin, mycophenolate mofetil, plasma exchange, and rituximab can be offered to patients who are intolerant or have a contraindication to cyclophosphamide. However, efficacy is unproven for any of these therapies. Interferon-alpha, sometimes combined with plasma exchange, is used to treat vasculitis associated with hepatitis B infection. Some patients also may improve with corticosteroids. The classification of diabetic lumbosacral radiculoplexus neuropathy as a vasculitic disorder remains controversial. However, there is compelling pathological evidence that this condition represents a T-cell-mediated microvasculitis. Some patients treated with intravenous corticosteroids may have greater recovery and improved pain control.

https://pubmed.ncbi.nlm.nih.gov/16464407/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Therapy for vasculitic neuropathies. The term vasculitis refers to a pathologic condition defined by inflammatory cell infiltration and destruction of blood vessels. Systemic vasculitis is classified as primary (eg, polyarteritis nodosa, Churg-Strauss syndrome) or secondary, the latter associated with connective tissue disorders, infections, medications, and rarely, as a paraneoplastic phenomenon. Neuropathy is a common complication of systemic vasculitis and is related to ischemic nerve fiber damage with axon loss. Peripheral neuropathy may be the sole manifestation of vasculitis, a condition termed nonsystemic vasculitic neuropathy (NSVN). Treatment of vasculitic neuropathy requires long-term immunosuppressive therapies with potential side effects. The diagnosis of vasculitis should be established by tissue (preferably nerve) biopsy. High-dose prednisone is the standard platform therapy for patients with systemic and NSVN; for those with systemic vasculitis, at least 3 to 12 months of treatment with cyclophosphamide (monthly intravenous pulse or daily oral therapy) is also necessary to sustain remission and allow successful prednisone tapering. The use of cyclophosphamide in patients with NSVN is controversial , but recent retrospective data suggest that those treated with prednisone and cyclophosphamide from the outset fare better than those initially treated only with prednisone . If prednisone is administered as monotherapy, cyclophosphamide should be added after several months if there is no improvement or relapse occurs with tapering of prednisone. Intravenous pulse and daily oral cyclophosphamide probably offer similar efficacy, although the risk of complications is greater with oral therapy. azathioprine can be safely substituted for cyclophosphamide after 3 months without an increased relapse rate. azathioprine, methotrexate, intravenous immune globulin, mycophenolate mofetil, plasma exchange, and rituximab can be offered to patients who are intolerant or have a contraindication to cyclophosphamide. However, efficacy is unproven for any of these therapies. Interferon-alpha, sometimes combined with plasma exchange, is used to treat vasculitis associated with hepatitis B infection. Some patients also may improve with corticosteroids. The classification of diabetic lumbosacral radiculoplexus neuropathy as a vasculitic disorder remains controversial. However, there is compelling pathological evidence that this condition represents a T-cell-mediated microvasculitis. Some patients treated with intravenous corticosteroids may have greater recovery and improved pain control. ### Response: cyclophosphamide, prednisone, cyclophosphamide, prednisone

5edd6b7bf1ec8e231328a5a83f5b82ae

This was a multi-center randomized , two-armed , double-blinded phase II study comparing cediranib plus gefitinib versus cediranib plus placebo in subjects with first relapse/first progression of glioblastoma following surgery and chemoradiotherapy .

Multi-Center Randomized Phase II Study Comparing Cediranib plus Gefitinib with Cediranib plus Placebo in Subjects with Recurrent/Progressive Glioblastoma. cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, failed to show benefit over lomustine in relapsed glioblastoma. One resistance mechanism for cediranib is up-regulation of epidermal growth factor receptor (EGFR). This study aimed to determine if dual therapy with cediranib and the oral EGFR inhibitor gefitinib improved outcome in recurrent glioblastoma. ### Methods And Findings This was a multi-center randomized , two-armed , double-blinded phase II study comparing cediranib plus gefitinib versus cediranib plus placebo in subjects with first relapse/first progression of glioblastoma following surgery and chemoradiotherapy . The primary outcome measure was progression free survival (PFS). Secondary outcome measures included overall survival (OS) and radiologic response rate. Recruitment was terminated early following suspension of the cediranib program. 38 subjects (112 planned) were enrolled with 19 subjects in each treatment arm. Median PFS with cediranib plus gefitinib was 3.6 months compared to 2.8 months for cediranib plus placebo (HR; 0.72, 90% CI; 0.41 to 1.26). Median OS was 7.2 months with cediranib plus gefitinib and 5.5 months with cediranib plus placebo (HR; 0.68, 90% CI; 0.39 to 1.19). Eight subjects (42%) had a partial response in the cediranib plus gefitinib arm versus five patients (26%) in the cediranib plus placebo arm. ### conclusions cediranib and gefitinib in combination is tolerated in patients with glioblastoma. Incomplete recruitment led to the study being underpowered. However, a trend towards improved survival and response rates with the addition of gefitinib to cediranib was observed. Further studies of the combination incorporating EGFR and VEGF inhibition are warranted. ### Trial Registration ClinicalTrials.gov NCT01310855.

https://pubmed.ncbi.nlm.nih.gov/27232884/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Multi-Center Randomized Phase II Study Comparing Cediranib plus Gefitinib with Cediranib plus Placebo in Subjects with Recurrent/Progressive Glioblastoma. cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, failed to show benefit over lomustine in relapsed glioblastoma. One resistance mechanism for cediranib is up-regulation of epidermal growth factor receptor (EGFR). This study aimed to determine if dual therapy with cediranib and the oral EGFR inhibitor gefitinib improved outcome in recurrent glioblastoma. ### Methods And Findings This was a multi-center randomized , two-armed , double-blinded phase II study comparing cediranib plus gefitinib versus cediranib plus placebo in subjects with first relapse/first progression of glioblastoma following surgery and chemoradiotherapy . The primary outcome measure was progression free survival (PFS). Secondary outcome measures included overall survival (OS) and radiologic response rate. Recruitment was terminated early following suspension of the cediranib program. 38 subjects (112 planned) were enrolled with 19 subjects in each treatment arm. Median PFS with cediranib plus gefitinib was 3.6 months compared to 2.8 months for cediranib plus placebo (HR; 0.72, 90% CI; 0.41 to 1.26). Median OS was 7.2 months with cediranib plus gefitinib and 5.5 months with cediranib plus placebo (HR; 0.68, 90% CI; 0.39 to 1.19). Eight subjects (42%) had a partial response in the cediranib plus gefitinib arm versus five patients (26%) in the cediranib plus placebo arm. ### conclusions cediranib and gefitinib in combination is tolerated in patients with glioblastoma. Incomplete recruitment led to the study being underpowered. However, a trend towards improved survival and response rates with the addition of gefitinib to cediranib was observed. Further studies of the combination incorporating EGFR and VEGF inhibition are warranted. ### Trial Registration ClinicalTrials.gov NCT01310855. ### Response: cediranib, gefitinib, cediranib

aef35abee464e3a0075caeb3d70926f6

This study aims to compare the biological , molecular , pharmacological , and clinical characteristics of these three treatment modalities for SARS-COV-2 infections , Chloroquine and Hydroxychloroquine , Convalescent Plasma , and Remdesivir .

Biological, molecular and pharmacological characteristics of chloroquine, hydroxychloroquine, convalescent plasma, and remdesivir for COVID-19 pandemic: A comparative analysis. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, also known as COVID-19 pandemic has caused an alarming situation worldwide. Since the first detection, in December 2019, there have been no effective drug therapy options for treating the SARS-CoV-2 pandemic. However, healthcare professionals are using chloroquine, hydroxychloroquine, remdesivir, convalescent plasma and some other options of treatments. This study aims to compare the biological , molecular , pharmacological , and clinical characteristics of these three treatment modalities for SARS-COV-2 infections , Chloroquine and Hydroxychloroquine , Convalescent Plasma , and Remdesivir . ### methods A search was conducted in the "Institute of Science Information (ISI)-Web of Science, PubMed, EMBASE, ClinicalTrials.gov, Cochrane Library databases, Scopus, and Google Scholar" for peer reviewed, published studies and clinical trials through July 30, 2020. The search was based on keywords "COVID-19" SARS-COV-2, chloroquine, hydroxychloroquine, convalescent plasma, remdesivir and treatment modalities. ### results As of July 30, 2020, a total of 36,640 relevant documents were published. From them 672 peer reviewed, published articles, and clinical trials were screened. We selected 17 relevant published original articles and clinical trials: 05 for chloroquine and/or hydroxychloroquine with total sample size (n = 220), 05 for remdesivir (n = 1,781), and 07 for Convalescent Plasma therapy (n = 398), with a combined total sample size (n = 2,399). Based on the available data, convalescent plasma therapy showed clinical advantages in SARS-COV-2 patients. ### conclusions All three treatment modalities have both favorable and unfavorable characteristics, but none showed clear evidence of benefit for early outpatient disease or prophylaxis. Based on the current available data, convalescent plasma therapy appears to show clinical advantages for inpatient use. In the future, ongoing large sample size randomized controlled clinical trials may further clarify the comparative efficacy and safety of these three treatment classes, to conclusively determine whom to treat with which drug and when to treat them.

https://pubmed.ncbi.nlm.nih.gov/32921965/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Biological, molecular and pharmacological characteristics of chloroquine, hydroxychloroquine, convalescent plasma, and remdesivir for COVID-19 pandemic: A comparative analysis. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, also known as COVID-19 pandemic has caused an alarming situation worldwide. Since the first detection, in December 2019, there have been no effective drug therapy options for treating the SARS-CoV-2 pandemic. However, healthcare professionals are using chloroquine, hydroxychloroquine, remdesivir, convalescent plasma and some other options of treatments. This study aims to compare the biological , molecular , pharmacological , and clinical characteristics of these three treatment modalities for SARS-COV-2 infections , Chloroquine and Hydroxychloroquine , Convalescent Plasma , and Remdesivir . ### methods A search was conducted in the "Institute of Science Information (ISI)-Web of Science, PubMed, EMBASE, ClinicalTrials.gov, Cochrane Library databases, Scopus, and Google Scholar" for peer reviewed, published studies and clinical trials through July 30, 2020. The search was based on keywords "COVID-19" SARS-COV-2, chloroquine, hydroxychloroquine, convalescent plasma, remdesivir and treatment modalities. ### results As of July 30, 2020, a total of 36,640 relevant documents were published. From them 672 peer reviewed, published articles, and clinical trials were screened. We selected 17 relevant published original articles and clinical trials: 05 for chloroquine and/or hydroxychloroquine with total sample size (n = 220), 05 for remdesivir (n = 1,781), and 07 for Convalescent Plasma therapy (n = 398), with a combined total sample size (n = 2,399). Based on the available data, convalescent plasma therapy showed clinical advantages in SARS-COV-2 patients. ### conclusions All three treatment modalities have both favorable and unfavorable characteristics, but none showed clear evidence of benefit for early outpatient disease or prophylaxis. Based on the current available data, convalescent plasma therapy appears to show clinical advantages for inpatient use. In the future, ongoing large sample size randomized controlled clinical trials may further clarify the comparative efficacy and safety of these three treatment classes, to conclusively determine whom to treat with which drug and when to treat them. ### Response: Chloroquine, Hydroxychloroquine, Remdesivir

be6dfc402b0da5cb965fc0a6da145866

Patients received a mean ( ±standard deviation ) of 8.8 ± 4.9 intravitreal bevacizumab injections prior to the switch to intravitreal ranibizumab .

Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel (DERBI study). To evaluate the outcome of second-line intravitreal ranibizumab treatment in eyes with diabetic macular edema having persistent edema following initial therapy with intravitreal bevacizumab. ### Methods Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel was a retrospective, multi-center study. Consecutive eyes with persistent diabetic macular edema following at least three previous intravitreal bevacizumab injections prior to intravitreal ranibizumab, at least three-monthly intravitreal ranibizumab injections and at least 12 months of follow-up were included. Data collected included demographics, ocular findings, diabetes control, details of intravitreal bevacizumab and ranibizumab injections, and visual and anatomical measurements before and after intravitreal ranibizumab treatment. ### Results In total, 202 eyes of 162 patients treated at 11 medical centers across Israel were included. Patients received a mean ( ±standard deviation ) of 8.8 ± 4.9 intravitreal bevacizumab injections prior to the switch to intravitreal ranibizumab . A mean of 7.0 ± 2.7 intravitreal ranibizumab injections were given during the 12 months following the switch to intravitreal ranibizumab. The median central subfield retinal thickness (±interquartile range) by spectral-domain optical coherence tomography decreased from 436 ± 162 µm at baseline to 319 ± 113 µm at month 12 (p < 0.001). Median logMAR visual acuity (±interquartile range) improved from 0.40 ± 0.48 at baseline to 0.38 ± 0.40 at month 12 (p = 0.001). Linear regression suggested that higher number of intravitreal ranibizumab injections and higher pre-switch central subfield retinal thickness were associated with favorable visual outcome. Higher number of intravitreal bevacizumab injections and the presence of intraretinal fluid before the switch lessened the odds of favorable outcome. ### Conclusion Switching from bevacizumab to ranibizumab in persistent diabetic macular edema was associated with anatomical improvement in the majority of eyes and ⩾2 lines of vision improvement in 22% of eyes.

https://pubmed.ncbi.nlm.nih.gov/29916263/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel (DERBI study). To evaluate the outcome of second-line intravitreal ranibizumab treatment in eyes with diabetic macular edema having persistent edema following initial therapy with intravitreal bevacizumab. ### Methods Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel was a retrospective, multi-center study. Consecutive eyes with persistent diabetic macular edema following at least three previous intravitreal bevacizumab injections prior to intravitreal ranibizumab, at least three-monthly intravitreal ranibizumab injections and at least 12 months of follow-up were included. Data collected included demographics, ocular findings, diabetes control, details of intravitreal bevacizumab and ranibizumab injections, and visual and anatomical measurements before and after intravitreal ranibizumab treatment. ### Results In total, 202 eyes of 162 patients treated at 11 medical centers across Israel were included. Patients received a mean ( ±standard deviation ) of 8.8 ± 4.9 intravitreal bevacizumab injections prior to the switch to intravitreal ranibizumab . A mean of 7.0 ± 2.7 intravitreal ranibizumab injections were given during the 12 months following the switch to intravitreal ranibizumab. The median central subfield retinal thickness (±interquartile range) by spectral-domain optical coherence tomography decreased from 436 ± 162 µm at baseline to 319 ± 113 µm at month 12 (p < 0.001). Median logMAR visual acuity (±interquartile range) improved from 0.40 ± 0.48 at baseline to 0.38 ± 0.40 at month 12 (p = 0.001). Linear regression suggested that higher number of intravitreal ranibizumab injections and higher pre-switch central subfield retinal thickness were associated with favorable visual outcome. Higher number of intravitreal bevacizumab injections and the presence of intraretinal fluid before the switch lessened the odds of favorable outcome. ### Conclusion Switching from bevacizumab to ranibizumab in persistent diabetic macular edema was associated with anatomical improvement in the majority of eyes and ⩾2 lines of vision improvement in 22% of eyes. ### Response: bevacizumab, ranibizumab

0a53b483acefa9c81b17bd994c27ddfd

Combinations of penicillin and streptomycin and penicillin and amikacin were synergistic only against those strains that were not highly resistant to streptomycin and kanamycin , respectively .

Species-specific resistance to antimocrobial synergism in Streptococcus faecium and Streptococcus faecalis. Combinations of penicillin with various aminoglycosidic aminocyclitols were tested against a collection of clinical isolates of Streptococcus faecium in vitro and were used to treat endocarditis caused by S. faecium in the rabbit model. S. faecium proved more resistant to penicillin than Streptococcus faecalis. Even more striking, however, was the resistance to in vitro synergism by combinations of penicillin and various aminoglycosides. At clinically achievable concentrations, penicillin-gentamicin was the only combination that was synergistic against all strains that were tested. Combinations of penicillin and streptomycin and penicillin and amikacin were synergistic only against those strains that were not highly resistant to streptomycin and kanamycin , respectively . Combinations of penicillin with kanamycin, tobramycin, sisomicin, or netilmicin failed to produce synergism against any of these strains. The possible clinical significance of these findings was verified by use of the rabbit model of endocarditis. Combinations of penicillin with gentamicin or streptomycin were synergistic in the therapy of endocarditis that was produced by a strain of S. faecium that did not have a high level of resistance to aminoglycosides. However, the combination of penicillin and netilmicin was no more effective than penicillin alone.

https://pubmed.ncbi.nlm.nih.gov/113469/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Species-specific resistance to antimocrobial synergism in Streptococcus faecium and Streptococcus faecalis. Combinations of penicillin with various aminoglycosidic aminocyclitols were tested against a collection of clinical isolates of Streptococcus faecium in vitro and were used to treat endocarditis caused by S. faecium in the rabbit model. S. faecium proved more resistant to penicillin than Streptococcus faecalis. Even more striking, however, was the resistance to in vitro synergism by combinations of penicillin and various aminoglycosides. At clinically achievable concentrations, penicillin-gentamicin was the only combination that was synergistic against all strains that were tested. Combinations of penicillin and streptomycin and penicillin and amikacin were synergistic only against those strains that were not highly resistant to streptomycin and kanamycin , respectively . Combinations of penicillin with kanamycin, tobramycin, sisomicin, or netilmicin failed to produce synergism against any of these strains. The possible clinical significance of these findings was verified by use of the rabbit model of endocarditis. Combinations of penicillin with gentamicin or streptomycin were synergistic in the therapy of endocarditis that was produced by a strain of S. faecium that did not have a high level of resistance to aminoglycosides. However, the combination of penicillin and netilmicin was no more effective than penicillin alone. ### Response: streptomycin, amikacin, streptomycin, kanamycin, penicillin, penicillin

7d64d6b1c7e8c6d3edc29168ad6c4477

Treatment with a combination chemotherapeutic regimen consisting of cyclophosphamide , vincristine , and dacarbazine for malignant paraganglioma with hepatic metastasis is reported .

Combination chemotherapy for malignant paraganglioma. Treatment with a combination chemotherapeutic regimen consisting of cyclophosphamide , vincristine , and dacarbazine for malignant paraganglioma with hepatic metastasis is reported . A 51-year-old male presented with tumors in the retroperitoneal space and liver. The patient was diagnosed as having paraganglioma based on elevated levels of serum neuron-specific enolase, urinary catecholamine and vanillylmandelic acid, and on histological findings of the liver specimen. The patient was treated with this combination chemotherapy in repeated 21-day cycles. Temporary improvement in laboratory findings and a 20% reduction in the size of the hepatic masses were observed without severe adverse effects.

https://pubmed.ncbi.nlm.nih.gov/9058098/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Combination chemotherapy for malignant paraganglioma. Treatment with a combination chemotherapeutic regimen consisting of cyclophosphamide , vincristine , and dacarbazine for malignant paraganglioma with hepatic metastasis is reported . A 51-year-old male presented with tumors in the retroperitoneal space and liver. The patient was diagnosed as having paraganglioma based on elevated levels of serum neuron-specific enolase, urinary catecholamine and vanillylmandelic acid, and on histological findings of the liver specimen. The patient was treated with this combination chemotherapy in repeated 21-day cycles. Temporary improvement in laboratory findings and a 20% reduction in the size of the hepatic masses were observed without severe adverse effects. ### Response: cyclophosphamide, vincristine, dacarbazine

498f31d903df63cf2f948946a8ee5018

The aim of this study was to evaluate the in vitro effect of single antibiotic ( ciprofloxacin , ceftazidime , or ampicillin ) treatment on adherence of Escherichia coli and Enterococcus to plastic stents .

In vitro evaluation of antibiotic prophylaxis in the prevention of biliary stent blockage. Bacterial adherence and biofilm formation are important factors in the blockage of biliary stents. Clinical studies with oral antibiotic prophylaxis to prevent stent blockage have produced conflicting results. The aim of this study was to evaluate the in vitro effect of single antibiotic ( ciprofloxacin , ceftazidime , or ampicillin ) treatment on adherence of Escherichia coli and Enterococcus to plastic stents . ### methods Selected clinical isolates of E coli and Enterococcus were perfused through a modified Robbins device containing segments of polyethylene stents. The stents were removed daily and the number of bacteria attached was measured. The effect of antibiotic treatment on bacterial adherence was tested by the perfusion of individual antibiotics into separate modified Robbins devices using a side-arm adaptor and the results were compared with saline controls. ### results Compared with the saline controls, ciprofloxacin and ceftazidime caused a 10- to 100-fold reduction in the number of E coli attached to the stents, whereas ampicillin had no effect on adherence of E coli. ampicillin caused a 5- to 10-fold reduction in Enterococcus adherence but there was no change with ceftazidime. Sustained reduction in E coli adherence was observed with prolonged ciprofloxacin perfusion. ### conclusion Timely treatment with appropriate antibiotics reduced bacterial adherence in vitro and may be potentially beneficial in the prevention of stent blockage.

https://pubmed.ncbi.nlm.nih.gov/10699774/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: In vitro evaluation of antibiotic prophylaxis in the prevention of biliary stent blockage. Bacterial adherence and biofilm formation are important factors in the blockage of biliary stents. Clinical studies with oral antibiotic prophylaxis to prevent stent blockage have produced conflicting results. The aim of this study was to evaluate the in vitro effect of single antibiotic ( ciprofloxacin , ceftazidime , or ampicillin ) treatment on adherence of Escherichia coli and Enterococcus to plastic stents . ### methods Selected clinical isolates of E coli and Enterococcus were perfused through a modified Robbins device containing segments of polyethylene stents. The stents were removed daily and the number of bacteria attached was measured. The effect of antibiotic treatment on bacterial adherence was tested by the perfusion of individual antibiotics into separate modified Robbins devices using a side-arm adaptor and the results were compared with saline controls. ### results Compared with the saline controls, ciprofloxacin and ceftazidime caused a 10- to 100-fold reduction in the number of E coli attached to the stents, whereas ampicillin had no effect on adherence of E coli. ampicillin caused a 5- to 10-fold reduction in Enterococcus adherence but there was no change with ceftazidime. Sustained reduction in E coli adherence was observed with prolonged ciprofloxacin perfusion. ### conclusion Timely treatment with appropriate antibiotics reduced bacterial adherence in vitro and may be potentially beneficial in the prevention of stent blockage. ### Response: ciprofloxacin, ceftazidime, ampicillin

717f8a8c20069d19d917002e078901ef

Paclitaxel and docetaxel as single agents have yielded overall response rates of 7 % to 56 % , depending on whether the patients have received prior chemotherapy for metastatic disease .

Current and future perspectives in advanced bladder cancer: is there a new standard? The methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) regimen has been the standard treatment in patients with locally advanced and metastatic urothelial cancer for the past 15 years. The minimal or moderate survival benefit-depending on prognostic features-and the severe toxicity associated with the MVAC regimen have made the search for new drugs and drug combinations of utmost importance to increase efficacy and/or decrease toxicity. In this respect, the taxanes and gemcitabine are promising new drugs. Paclitaxel and docetaxel as single agents have yielded overall response rates of 7 % to 56 % , depending on whether the patients have received prior chemotherapy for metastatic disease . The combination of paclitaxel and cisplatin has been explored in three studies with a total of 104 evaluable patients, a pooled overall response (OR) rate of 61%, and a complete response (CR) rate of 20%. There are two studies of docetaxel and cisplatin with a total of 91 evaluable patients, an OR rate of 54%, and a CR rate of 16%. The OR rate for paclitaxel and carboplatin in six studies was 43%, with a CR rate of 13%; however, the reported median survival was only 8.5 to 9.5 months. The OR rate for single-agent gemcitabine based on five studies was 26%, with a CR rate of 9%, which was apparently independent of whether the patients had received prior chemotherapy. The OR rate for gemcitabine and cisplatin in four phase II studies ranged from 41% to 57%, with a CR rate of 15% to 22% and a median survival of 12.5 to 14.3 months. Based on the encouraging results for the combination of gemcitabine and cisplatin (GC), a randomized phase III trial comparing GC and MVAC was begun in late 1996. This study of 405 randomized patients showed that the two regimens were associated with similar response rates, time to progression, and overall survival, whereas GC was associated with less toxicity than MVAC. On the basis of this superior risk-benefit ratio, the GC regimen should be favored as a new standard treatment in patients with locally advanced and metastatic urothelial cancer. Other promising combinations include gemcitabine and paclitaxel, with or without cisplatin, and the combination of ifosfamide, paclitaxel, and cisplatin. The triple combination of gemcitabine, paclitaxel, and cisplatin has yielded an OR rate of 78%, a CR rate of 28%, and a median survival of 24 months. An international phase III trial comparing this triple combination with GC in patients with locally advanced and metastatic urothelial cancer has now been initiated.

https://pubmed.ncbi.nlm.nih.gov/11894002/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Current and future perspectives in advanced bladder cancer: is there a new standard? The methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) regimen has been the standard treatment in patients with locally advanced and metastatic urothelial cancer for the past 15 years. The minimal or moderate survival benefit-depending on prognostic features-and the severe toxicity associated with the MVAC regimen have made the search for new drugs and drug combinations of utmost importance to increase efficacy and/or decrease toxicity. In this respect, the taxanes and gemcitabine are promising new drugs. Paclitaxel and docetaxel as single agents have yielded overall response rates of 7 % to 56 % , depending on whether the patients have received prior chemotherapy for metastatic disease . The combination of paclitaxel and cisplatin has been explored in three studies with a total of 104 evaluable patients, a pooled overall response (OR) rate of 61%, and a complete response (CR) rate of 20%. There are two studies of docetaxel and cisplatin with a total of 91 evaluable patients, an OR rate of 54%, and a CR rate of 16%. The OR rate for paclitaxel and carboplatin in six studies was 43%, with a CR rate of 13%; however, the reported median survival was only 8.5 to 9.5 months. The OR rate for single-agent gemcitabine based on five studies was 26%, with a CR rate of 9%, which was apparently independent of whether the patients had received prior chemotherapy. The OR rate for gemcitabine and cisplatin in four phase II studies ranged from 41% to 57%, with a CR rate of 15% to 22% and a median survival of 12.5 to 14.3 months. Based on the encouraging results for the combination of gemcitabine and cisplatin (GC), a randomized phase III trial comparing GC and MVAC was begun in late 1996. This study of 405 randomized patients showed that the two regimens were associated with similar response rates, time to progression, and overall survival, whereas GC was associated with less toxicity than MVAC. On the basis of this superior risk-benefit ratio, the GC regimen should be favored as a new standard treatment in patients with locally advanced and metastatic urothelial cancer. Other promising combinations include gemcitabine and paclitaxel, with or without cisplatin, and the combination of ifosfamide, paclitaxel, and cisplatin. The triple combination of gemcitabine, paclitaxel, and cisplatin has yielded an OR rate of 78%, a CR rate of 28%, and a median survival of 24 months. An international phase III trial comparing this triple combination with GC in patients with locally advanced and metastatic urothelial cancer has now been initiated. ### Response: Paclitaxel, docetaxel

a963d46b799a8ea638850359444188f9

The most effective treatment regimens for advanced nonseminomatous testicular tumors employ vinblastine , CDDP and bleomycin and adjunctive surgery .

[Preoperative chemotherapy of testicular cancer and Wilm's tumor]. Of the various urogenital malignancies, preoperative chemotherapy is most effective for testicular cancer and Wilms' tumor. The most effective treatment regimens for advanced nonseminomatous testicular tumors employ vinblastine , CDDP and bleomycin and adjunctive surgery . Another effective chemotherapy regimen is combination of vinblastine, actinomycin D, bleomycin, cyclophosphamide and CDDP presented by MSKCC. Available pretreatment with 4 courses of platinum, vinblastine and bleomycin before any surgical treatment in those with massive bulk metastatic disease seems to provide the most effective cytoreduction and best survival. Donohue has shown that in a primary chemotherapy group, there is only 20% active carcinoma after primary chemotherapy, whereas in a salvage chemotherapy group there is approximately 50% active carcinoma at surgery. It must therefore be emphasized that complete remission should be obtained by primary chemotherapy and adjunctive surgery. In Wilms' tumor preoperative chemotherapy with vincristine and actinomycin D should be given.

https://pubmed.ncbi.nlm.nih.gov/2581512/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: [Preoperative chemotherapy of testicular cancer and Wilm's tumor]. Of the various urogenital malignancies, preoperative chemotherapy is most effective for testicular cancer and Wilms' tumor. The most effective treatment regimens for advanced nonseminomatous testicular tumors employ vinblastine , CDDP and bleomycin and adjunctive surgery . Another effective chemotherapy regimen is combination of vinblastine, actinomycin D, bleomycin, cyclophosphamide and CDDP presented by MSKCC. Available pretreatment with 4 courses of platinum, vinblastine and bleomycin before any surgical treatment in those with massive bulk metastatic disease seems to provide the most effective cytoreduction and best survival. Donohue has shown that in a primary chemotherapy group, there is only 20% active carcinoma after primary chemotherapy, whereas in a salvage chemotherapy group there is approximately 50% active carcinoma at surgery. It must therefore be emphasized that complete remission should be obtained by primary chemotherapy and adjunctive surgery. In Wilms' tumor preoperative chemotherapy with vincristine and actinomycin D should be given. ### Response: vinblastine, bleomycin

773651170795da523779ad0a4d8fdd24

27 patients suffering from disseminated carcinoma of the breast with at least two visceral metastases , and two had become resistant to conventional chemotherpy and hormones , received a combination of , in the present trial , vincristine followed by cyclophosphamide with 5-fluoro-uracil .

[Chemotherapeutic combinations of mutually potentializing drugs. 1-Application to the treatment of breast cancers]. 27 patients suffering from disseminated carcinoma of the breast with at least two visceral metastases , and two had become resistant to conventional chemotherpy and hormones , received a combination of , in the present trial , vincristine followed by cyclophosphamide with 5-fluoro-uracil . Chemotherapy was administered intermittently: each cycle of treatment lasted 6 days and was followed by a period without treatment of 25 days. Haematological tolerance was satisfactory. No serious incidents occurred during two years use of the combination. 20 out of 27 patients showed objective tumour regression of more than 50 p.cent lasting for more than 6 months, whilst 9 showed apparent complete regression of the malignant lesions. There was one complete failure. Chemotherapy was continued in all cases after regression of the neoplastic process was obtained.

https://pubmed.ncbi.nlm.nih.gov/1129034/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: [Chemotherapeutic combinations of mutually potentializing drugs. 1-Application to the treatment of breast cancers]. 27 patients suffering from disseminated carcinoma of the breast with at least two visceral metastases , and two had become resistant to conventional chemotherpy and hormones , received a combination of , in the present trial , vincristine followed by cyclophosphamide with 5-fluoro-uracil . Chemotherapy was administered intermittently: each cycle of treatment lasted 6 days and was followed by a period without treatment of 25 days. Haematological tolerance was satisfactory. No serious incidents occurred during two years use of the combination. 20 out of 27 patients showed objective tumour regression of more than 50 p.cent lasting for more than 6 months, whilst 9 showed apparent complete regression of the malignant lesions. There was one complete failure. Chemotherapy was continued in all cases after regression of the neoplastic process was obtained. ### Response: vincristine, cyclophosphamide, 5-fluoro-uracil

8a164fc8cdf186bd07aed353d735c00b

We previously demonstrated that the combination of oral estramustine ( 15 mg/kg/day ) and oral etoposide ( 50 mg/m2/day ) is effective first-line therapy for the treatment of hormone refractory prostate cancer .

A phase II trial of oral estramustine and oral etoposide in hormone refractory prostate cancer. We previously demonstrated that the combination of oral estramustine ( 15 mg/kg/day ) and oral etoposide ( 50 mg/m2/day ) is effective first-line therapy for the treatment of hormone refractory prostate cancer . We initiated a new Phase II trial utilizing a lower dose of estramustine (10 mg/kg/day) and allowing previous chemotherapy treatment. ### methods estramustine (10 mg/kg/day) and etoposide (50 mg/m2/day) were administered orally for 21 of 28 days. Sixty-two patients were enrolled with a minimum of 26 weeks of follow-up. ### results Of 15 patients with measurable soft tissue disease, 8 (53%) had a partial response (PR). Seven of these 8 patients also demonstrated a decrease in baseline prostate-specific antigen (PSA) of more than 50%. The median survival of all patients was 56 weeks. Of 47 patients with disease limited to the bone, 16 (34%) had a PR to therapy based on decrease in pretreatment PSA of more than 50%. Overall, 24 (39%) of 62 patients demonstrated a decrease in pretreatment PSA levels of at least 50% from baseline. Twenty-two patients received previous chemotherapy. There were no differences in survival or disease response in patients treated with previous chemotherapy compared with untreated patients. Pretreatment hemoglobin, PSA, alkaline phosphatase and lactate dehydrogenase levels were not significant prognostic factors, but performance status was an important predictor of survival. ### conclusions We conclude that the combination of oral estramustine (10 mg/kg/day) and oral etoposide (50 mg/m2/day) is an active regimen for hormone refractory prostate cancer.

https://pubmed.ncbi.nlm.nih.gov/9301705/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: A phase II trial of oral estramustine and oral etoposide in hormone refractory prostate cancer. We previously demonstrated that the combination of oral estramustine ( 15 mg/kg/day ) and oral etoposide ( 50 mg/m2/day ) is effective first-line therapy for the treatment of hormone refractory prostate cancer . We initiated a new Phase II trial utilizing a lower dose of estramustine (10 mg/kg/day) and allowing previous chemotherapy treatment. ### methods estramustine (10 mg/kg/day) and etoposide (50 mg/m2/day) were administered orally for 21 of 28 days. Sixty-two patients were enrolled with a minimum of 26 weeks of follow-up. ### results Of 15 patients with measurable soft tissue disease, 8 (53%) had a partial response (PR). Seven of these 8 patients also demonstrated a decrease in baseline prostate-specific antigen (PSA) of more than 50%. The median survival of all patients was 56 weeks. Of 47 patients with disease limited to the bone, 16 (34%) had a PR to therapy based on decrease in pretreatment PSA of more than 50%. Overall, 24 (39%) of 62 patients demonstrated a decrease in pretreatment PSA levels of at least 50% from baseline. Twenty-two patients received previous chemotherapy. There were no differences in survival or disease response in patients treated with previous chemotherapy compared with untreated patients. Pretreatment hemoglobin, PSA, alkaline phosphatase and lactate dehydrogenase levels were not significant prognostic factors, but performance status was an important predictor of survival. ### conclusions We conclude that the combination of oral estramustine (10 mg/kg/day) and oral etoposide (50 mg/m2/day) is an active regimen for hormone refractory prostate cancer. ### Response: estramustine, etoposide

3065e65032c8537a0d4a53be07e8519a

Therapy consisted of bendamustine ( 70 mg/m(2 ) ) for 2 consecutive days every 28 days , and ofatumumab 300 mg on day 1 and 1000 mg on day 8 during the first cycle , and 1000 mg on day 1 subsequently .

Bendamustine in combination with ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II Trial. We conducted a phase II, noncomparative, open-label, multicenter GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) study (CLL0809) to assess the efficacy and safety of bendamustine in combination with ofatumumab (BendOfa) in relapsed/refractory chronic lymphocytic leukemia (CLL). Forty-seven patients from 14 centers were evaluated. Therapy consisted of bendamustine ( 70 mg/m(2 ) ) for 2 consecutive days every 28 days , and ofatumumab 300 mg on day 1 and 1000 mg on day 8 during the first cycle , and 1000 mg on day 1 subsequently . Treatment was administered up to six cycles. The overall response rate (ORR), as per intention-to-treat analysis, was 72.3% (95% confidence of interval (CI), 57-84%), with 17% complete responses. After a median follow-up of 24.2 months, the overall survival was 83.6% (95% CI, 73.0-95.7%) and the progression-free survival (PFS) was 49.6% (95% CI, 35.9-68.6%). The median PFS was 23.6 months. Univariate and multivariate analyses were used to identify clinical and biological characteristics associated with ORR and PFS. Myelosuppression was the most common toxicity; grade ≥3 neutropenia was observed in 61.7% of patients; however, grade ≥3 infections occurred in 6% of patients. BendOfa is feasible and effective in relapsed/refractory CLL patients, including patients with high-risk clinical and biological features.

https://pubmed.ncbi.nlm.nih.gov/24220274/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Bendamustine in combination with ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II Trial. We conducted a phase II, noncomparative, open-label, multicenter GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) study (CLL0809) to assess the efficacy and safety of bendamustine in combination with ofatumumab (BendOfa) in relapsed/refractory chronic lymphocytic leukemia (CLL). Forty-seven patients from 14 centers were evaluated. Therapy consisted of bendamustine ( 70 mg/m(2 ) ) for 2 consecutive days every 28 days , and ofatumumab 300 mg on day 1 and 1000 mg on day 8 during the first cycle , and 1000 mg on day 1 subsequently . Treatment was administered up to six cycles. The overall response rate (ORR), as per intention-to-treat analysis, was 72.3% (95% confidence of interval (CI), 57-84%), with 17% complete responses. After a median follow-up of 24.2 months, the overall survival was 83.6% (95% CI, 73.0-95.7%) and the progression-free survival (PFS) was 49.6% (95% CI, 35.9-68.6%). The median PFS was 23.6 months. Univariate and multivariate analyses were used to identify clinical and biological characteristics associated with ORR and PFS. Myelosuppression was the most common toxicity; grade ≥3 neutropenia was observed in 61.7% of patients; however, grade ≥3 infections occurred in 6% of patients. BendOfa is feasible and effective in relapsed/refractory CLL patients, including patients with high-risk clinical and biological features. ### Response: bendamustine, ofatumumab

304fb876f9dfa960295aef5a6099c04b

All consecutive patients with advanced BTC received the GEMOX regimen in a setting outside a study : gemcitabine 1,000 mg/m(2 ) on day 1 , and oxaliplatin 100 mg/m(2 ) on day 2 , treatment repeated every 2 weeks until progression or unacceptable toxicity .

Experience of gemcitabine plus oxaliplatin chemotherapy in patients with advanced biliary tract carcinoma. The combination gemcitabine-oxaliplatin (GEMOX) is frequently used in patients with advanced biliary tract carcinoma (BTC). However, this is only based on phase II studies performed in selected patients.We assessed the efficacy and safety of the GEMOX regimen in non-selected patients with advanced BTC. ### methods All consecutive patients with advanced BTC received the GEMOX regimen in a setting outside a study : gemcitabine 1,000 mg/m(2 ) on day 1 , and oxaliplatin 100 mg/m(2 ) on day 2 , treatment repeated every 2 weeks until progression or unacceptable toxicity . ### results Forty-four patients were enrolled. ### efficacy 1 complete and 6 partial responses (objective response rate = 16.3%), 18 tumour stabilizations (41.9%, disease control rate = 58.1%), median progression-free survival was 5.0 months and median overall survival was 11.0 months. ### toxicity grade 3 neuropathy in 4 patients, grade 3 asthenia in 5 patients. ### conclusion The GEMOX combination was well tolerated, with a modest activity in non-selected patients with advanced BTC. This regimen should be compared to the new standard gemcitabine-cisplatin combination.

https://pubmed.ncbi.nlm.nih.gov/20551640/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Experience of gemcitabine plus oxaliplatin chemotherapy in patients with advanced biliary tract carcinoma. The combination gemcitabine-oxaliplatin (GEMOX) is frequently used in patients with advanced biliary tract carcinoma (BTC). However, this is only based on phase II studies performed in selected patients.We assessed the efficacy and safety of the GEMOX regimen in non-selected patients with advanced BTC. ### methods All consecutive patients with advanced BTC received the GEMOX regimen in a setting outside a study : gemcitabine 1,000 mg/m(2 ) on day 1 , and oxaliplatin 100 mg/m(2 ) on day 2 , treatment repeated every 2 weeks until progression or unacceptable toxicity . ### results Forty-four patients were enrolled. ### efficacy 1 complete and 6 partial responses (objective response rate = 16.3%), 18 tumour stabilizations (41.9%, disease control rate = 58.1%), median progression-free survival was 5.0 months and median overall survival was 11.0 months. ### toxicity grade 3 neuropathy in 4 patients, grade 3 asthenia in 5 patients. ### conclusion The GEMOX combination was well tolerated, with a modest activity in non-selected patients with advanced BTC. This regimen should be compared to the new standard gemcitabine-cisplatin combination. ### Response: gemcitabine, oxaliplatin

70bd47165d708bee82beff55a73c29fc

Recent randomized controlled trials ( RCT ) have failed to demonstrate the efficacy of widely used therapies , such as rituximab plus intravenous immunoglobulin or proteasome inhibition ( bortezomib ) , reinforcing a great need for new therapeutic concepts .

Clazakizumab in late antibody-mediated rejection: study protocol of a randomized controlled pilot trial. Late antibody-mediated rejection (ABMR) triggered by donor-specific antibodies (DSA) is a cardinal cause of kidney allograft dysfunction and loss. Diagnostic criteria for this rejection type are well established, but effective treatment remains a major challenge. Recent randomized controlled trials ( RCT ) have failed to demonstrate the efficacy of widely used therapies , such as rituximab plus intravenous immunoglobulin or proteasome inhibition ( bortezomib ) , reinforcing a great need for new therapeutic concepts . One promising target in this context may be interleukin-6 (IL-6), a pleiotropic cytokine known to play an important role in inflammation and adaptive immunity. ### methods This investigator-driven RCT was designed to assess the safety and efficacy of clazakizumab, a genetically engineered humanized monoclonal antibody directed against IL-6. The study will include 20 DSA-positive kidney allograft recipients diagnosed with ABMR ≥ 365 days after transplantation. Participants will be recruited at two study sites in Austria and Germany (Medical University of Vienna; Charité University Medicine Berlin). First, patients will enter a three-month double-blind RCT (1,1 randomization, stratification according to ABMR phenotype and study site) and will receive either clazakizumab (subcutaneous administration of 25 mg in monthly intervals) or placebo. In a second open-label part of the trial (months 4-12), all patients will receive clazakizumab at 25 mg every month. The primary endpoint is safety and tolerability. Secondary endpoints are the pharmacokinetics and pharmacodynamics of clazakizumab, its effect on drug metabolism in the liver, DSA characteristics, morphological ABMR lesions and molecular gene expression patterns in three- and 12-month protocol biopsies, serum/urinary biomarkers of inflammation and endothelial activation/injury, Torque Teno viral load as a measure of overall immunosuppression, kidney function, urinary protein excretion, as well as transplant and patient survival. ### discussion Currently, there is no treatment proven to be effective in halting the progression of late ABMR. Based on the hypothesis that antagonizing the effects of IL-6 improves the outcome of DSA-positive late ABMR by counteracting DSA-triggered inflammation and B cell/plasma cell-driven alloimmunity, we suggest that our trial has the potential to provide proof of concept of a novel treatment of this type of rejection. ### Trial Registration ClinicalTrials.gov, NCT03444103 . Registered on 23 February 2018 (retrospective registration).

https://pubmed.ncbi.nlm.nih.gov/30635033/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Clazakizumab in late antibody-mediated rejection: study protocol of a randomized controlled pilot trial. Late antibody-mediated rejection (ABMR) triggered by donor-specific antibodies (DSA) is a cardinal cause of kidney allograft dysfunction and loss. Diagnostic criteria for this rejection type are well established, but effective treatment remains a major challenge. Recent randomized controlled trials ( RCT ) have failed to demonstrate the efficacy of widely used therapies , such as rituximab plus intravenous immunoglobulin or proteasome inhibition ( bortezomib ) , reinforcing a great need for new therapeutic concepts . One promising target in this context may be interleukin-6 (IL-6), a pleiotropic cytokine known to play an important role in inflammation and adaptive immunity. ### methods This investigator-driven RCT was designed to assess the safety and efficacy of clazakizumab, a genetically engineered humanized monoclonal antibody directed against IL-6. The study will include 20 DSA-positive kidney allograft recipients diagnosed with ABMR ≥ 365 days after transplantation. Participants will be recruited at two study sites in Austria and Germany (Medical University of Vienna; Charité University Medicine Berlin). First, patients will enter a three-month double-blind RCT (1,1 randomization, stratification according to ABMR phenotype and study site) and will receive either clazakizumab (subcutaneous administration of 25 mg in monthly intervals) or placebo. In a second open-label part of the trial (months 4-12), all patients will receive clazakizumab at 25 mg every month. The primary endpoint is safety and tolerability. Secondary endpoints are the pharmacokinetics and pharmacodynamics of clazakizumab, its effect on drug metabolism in the liver, DSA characteristics, morphological ABMR lesions and molecular gene expression patterns in three- and 12-month protocol biopsies, serum/urinary biomarkers of inflammation and endothelial activation/injury, Torque Teno viral load as a measure of overall immunosuppression, kidney function, urinary protein excretion, as well as transplant and patient survival. ### discussion Currently, there is no treatment proven to be effective in halting the progression of late ABMR. Based on the hypothesis that antagonizing the effects of IL-6 improves the outcome of DSA-positive late ABMR by counteracting DSA-triggered inflammation and B cell/plasma cell-driven alloimmunity, we suggest that our trial has the potential to provide proof of concept of a novel treatment of this type of rejection. ### Trial Registration ClinicalTrials.gov, NCT03444103 . Registered on 23 February 2018 (retrospective registration). ### Response: rituximab, intravenous immunoglobulin, bortezomib

42c1681f652cf35adf1ced53b97516f8

The aim of this study was to find an experimental model of a donor-recipient rat strain combination that , under triple drug immunosuppressive treatment ( methylprednisolone , cyclosporine , and azathioprine ) , would develop chronic rejection within a few weeks .

An experimental model of chronic renal allograft rejection in the rat using triple drug immunosuppression. Chronic rejection is a major problem in renal transplantation. Various experimental models have been developed to study vasculopathy of chronic rejection. However, animal models resembling the clinical situation of renal transplantation with combination therapy of basic immunosuppression are not available. The aim of this study was to find an experimental model of a donor-recipient rat strain combination that , under triple drug immunosuppressive treatment ( methylprednisolone , cyclosporine , and azathioprine ) , would develop chronic rejection within a few weeks . ### methods Renal transplantations were performed in strain combinations of DA-->AO, PVG-->BN, and DA-->BN. In each group, 5-8 animals received triple drug treatment of methylprednisolone (2 mg/kg), azathioprine (2 mg/kg), and cyclosporine (5 mg/kg) daily, 5-10 animals were left without treatment, and 6 syngenic transplantations were performed. The grafts were monitored with ultrasound-guided fine needle aspiration biopsies to quantify the inflammation in the graft. Graft histology was performed in parallel and quantified by using the chronic allograft damage index (CADI). ### results In nonimmunosuppressed animals, irreversible acute rejection with a high peak of inflammation appeared in every strain combination within 5-8 days. In triple drug-treated rats, the DA-->AO combination demonstrated a prolonged acute rejection but no characteristic chronic changes, and the PVG-->BN combination showed practically no inflammation and did not develop any signs of chronic rejection within 60 days (CADI: 2.7+/-2.1), but the DA-->BN combination showed an early, mild inflammatory response 5-7 days after transplantation and developed chronic rejection within 40-60 days after transplantation (CADI: 7.9+/-3.1). Syngenic animals showed no inflammation or histological alterations (CADI: 1.7+/-2.0). ### conclusions In conclusion, in the DA-->BN combination with triple drug treatment, early mild inflammation was followed by the development of chronic rejection and can be used as an experimental model that resembles the clinical situation in renal transplantation.

https://pubmed.ncbi.nlm.nih.gov/9448142/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: An experimental model of chronic renal allograft rejection in the rat using triple drug immunosuppression. Chronic rejection is a major problem in renal transplantation. Various experimental models have been developed to study vasculopathy of chronic rejection. However, animal models resembling the clinical situation of renal transplantation with combination therapy of basic immunosuppression are not available. The aim of this study was to find an experimental model of a donor-recipient rat strain combination that , under triple drug immunosuppressive treatment ( methylprednisolone , cyclosporine , and azathioprine ) , would develop chronic rejection within a few weeks . ### methods Renal transplantations were performed in strain combinations of DA-->AO, PVG-->BN, and DA-->BN. In each group, 5-8 animals received triple drug treatment of methylprednisolone (2 mg/kg), azathioprine (2 mg/kg), and cyclosporine (5 mg/kg) daily, 5-10 animals were left without treatment, and 6 syngenic transplantations were performed. The grafts were monitored with ultrasound-guided fine needle aspiration biopsies to quantify the inflammation in the graft. Graft histology was performed in parallel and quantified by using the chronic allograft damage index (CADI). ### results In nonimmunosuppressed animals, irreversible acute rejection with a high peak of inflammation appeared in every strain combination within 5-8 days. In triple drug-treated rats, the DA-->AO combination demonstrated a prolonged acute rejection but no characteristic chronic changes, and the PVG-->BN combination showed practically no inflammation and did not develop any signs of chronic rejection within 60 days (CADI: 2.7+/-2.1), but the DA-->BN combination showed an early, mild inflammatory response 5-7 days after transplantation and developed chronic rejection within 40-60 days after transplantation (CADI: 7.9+/-3.1). Syngenic animals showed no inflammation or histological alterations (CADI: 1.7+/-2.0). ### conclusions In conclusion, in the DA-->BN combination with triple drug treatment, early mild inflammation was followed by the development of chronic rejection and can be used as an experimental model that resembles the clinical situation in renal transplantation. ### Response: methylprednisolone, cyclosporine, azathioprine

373bedaa15b826ea4c469e0ce2643608

In FOLL05 trial , R-CHOP was compared with R-CVP ( cyclophosphamide , vincristine , prednisone ) and R-FM ( fludarabine , mitoxantrone ) .

Rituximab and new regimens for indolent lymphoma: a brief update from 2012 ASCO Annual Meeting. Indolent lymphoma (IL), the second most common lymphoma, remains incurable with chemotherapy alone. While R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) remains the standard frontline regimen for diffuse Large B -cell lymphoma, the optimal chemotherapy regimen for frontline therapy of advanced IL remains uncertain. FCR (fludarabine, cyclophosphamide, rituximab) has been shown to be better than fludarabine alone and fludarabine plus cyclophosphamide for IL. In FOLL05 trial , R-CHOP was compared with R-CVP ( cyclophosphamide , vincristine , prednisone ) and R-FM ( fludarabine , mitoxantrone ) . The study showed that R-CHOP appears to have the best risk-benefit ratio for IL. The StiL NHL1 trial showed that BR (bendamustine, rituximab) has longer progression free survival and is better tolerated than R-CHOP. Long-term complications with secondary malignancies between the two regimens appear to be comparable. In this review, new combination regimens reported at 2012 ASCO annual meeting were evaluated for frontline and salvage therapy of indolent lymphoma.

https://pubmed.ncbi.nlm.nih.gov/22913602/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Rituximab and new regimens for indolent lymphoma: a brief update from 2012 ASCO Annual Meeting. Indolent lymphoma (IL), the second most common lymphoma, remains incurable with chemotherapy alone. While R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) remains the standard frontline regimen for diffuse Large B -cell lymphoma, the optimal chemotherapy regimen for frontline therapy of advanced IL remains uncertain. FCR (fludarabine, cyclophosphamide, rituximab) has been shown to be better than fludarabine alone and fludarabine plus cyclophosphamide for IL. In FOLL05 trial , R-CHOP was compared with R-CVP ( cyclophosphamide , vincristine , prednisone ) and R-FM ( fludarabine , mitoxantrone ) . The study showed that R-CHOP appears to have the best risk-benefit ratio for IL. The StiL NHL1 trial showed that BR (bendamustine, rituximab) has longer progression free survival and is better tolerated than R-CHOP. Long-term complications with secondary malignancies between the two regimens appear to be comparable. In this review, new combination regimens reported at 2012 ASCO annual meeting were evaluated for frontline and salvage therapy of indolent lymphoma. ### Response: R-CHOP, cyclophosphamide, vincristine, prednisone, fludarabine, mitoxantrone

a4a83ba48665f39aac03658bbacb486b

All patients underwent 3 cycles of neoadjuvant gemcitabine , paclitaxel , and capecitabine .

Direct percutaneous transhepatic portomesenteric venous stenting in management of locally advanced pancreatic cancer. Pancreatectomy with portal and/or superior mesenteric vein resection remains a controversial procedure because of high complexity and morbidity. Neoadjuvant chemotherapy has been shown to increase resectability of these locally advanced lesions. We aimed to assess the utility and efficacy of direct percutaneous transhepatic portomesenteric venous stenting (THVS) with neoadjuvant chemotherapy in increasing surgical resectability of locally advanced pancreatic carcinoma. ### methods Forty pancreatic carcinoma patients with tumor thrombus involving the portal vein and superior mesenteric vein were identified. Patients underwent THVS followed by neoadjuvant chemotherapy. Whipple procedure was offered to responders. ### results THVS was attempted in all. The tumor thrombus could not be crossed in 2 patients (95% technical success rate). All patients underwent 3 cycles of neoadjuvant gemcitabine , paclitaxel , and capecitabine . Disease progression was noted in 16 patients and surgery was not offered. Twenty-two patients were explored with intent-to-perform a Whipple procedure. In 7 of these (32%), extensive disease precluding surgical resection was identified and the procedure was abandoned. Whipple procedure without vascular resection was performed successfully in 15 patients (68%). There were no perioperative deaths. Negative vascular margins were noted in 3 patients and negative peripancreatic lymph nodes in 5 patients. Median survival was 17 months (range, 5 to 70 mo). In the stented nonoperative group, median survival was 9 months (range, 3 to 19 mo). The stented and resected group achieved a statistically significant (P=0.0422) survival advantage. ### conclusions THVS in combination with neoadjuvant chemotherapy can increase tumor resectability and survival in a select group of locally advanced pancreatic cancer patients.

https://pubmed.ncbi.nlm.nih.gov/23608832/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Direct percutaneous transhepatic portomesenteric venous stenting in management of locally advanced pancreatic cancer. Pancreatectomy with portal and/or superior mesenteric vein resection remains a controversial procedure because of high complexity and morbidity. Neoadjuvant chemotherapy has been shown to increase resectability of these locally advanced lesions. We aimed to assess the utility and efficacy of direct percutaneous transhepatic portomesenteric venous stenting (THVS) with neoadjuvant chemotherapy in increasing surgical resectability of locally advanced pancreatic carcinoma. ### methods Forty pancreatic carcinoma patients with tumor thrombus involving the portal vein and superior mesenteric vein were identified. Patients underwent THVS followed by neoadjuvant chemotherapy. Whipple procedure was offered to responders. ### results THVS was attempted in all. The tumor thrombus could not be crossed in 2 patients (95% technical success rate). All patients underwent 3 cycles of neoadjuvant gemcitabine , paclitaxel , and capecitabine . Disease progression was noted in 16 patients and surgery was not offered. Twenty-two patients were explored with intent-to-perform a Whipple procedure. In 7 of these (32%), extensive disease precluding surgical resection was identified and the procedure was abandoned. Whipple procedure without vascular resection was performed successfully in 15 patients (68%). There were no perioperative deaths. Negative vascular margins were noted in 3 patients and negative peripancreatic lymph nodes in 5 patients. Median survival was 17 months (range, 5 to 70 mo). In the stented nonoperative group, median survival was 9 months (range, 3 to 19 mo). The stented and resected group achieved a statistically significant (P=0.0422) survival advantage. ### conclusions THVS in combination with neoadjuvant chemotherapy can increase tumor resectability and survival in a select group of locally advanced pancreatic cancer patients. ### Response: gemcitabine, paclitaxel, capecitabine

509f0b830dc248843856cc659af95634

The aim of the present investigation was to study and characterize the effect of voriconazole on the fungicidal activity of amphotericin B.

Characterization of the inhibitory effect of voriconazole on the fungicidal activity of amphotericin B against Candida albicans in an in vitro kinetic model. The aim of the present investigation was to study and characterize the effect of voriconazole on the fungicidal activity of amphotericin B. ### methods Four strains of Candida albicans susceptible to voriconazole were exposed to voriconazole and amphotericin B, either alone, simultaneously or sequentially in an in vitro kinetic model. Bolus doses resulting in voriconazole and amphotericin B concentrations of 0.005-5 and 2.5 mg/L, respectively, were administered. Antifungal-containing RPMI 1640 was eliminated and replaced by a fresh medium using a peristaltic pump, with a flow rate adjusted to obtain the desired half-lives. With two drugs tested, a computer-controlled dosing pump compensated for differences in the elimination rates. Using static time-kill methodology, one C. albicans strain was exposed to 5 mg/L voriconazole for varying durations followed by 2.5 mg/L amphotericin B after three repeated washes of voriconazole. ### results voriconazole and amphotericin B treatment alone resulted in fungistatic and fungicidal activities, respectively. Simultaneous administration of voriconazole and amphotericin B resulted in fungicidal activity, whereas only fungistatic activity was observed when repeated doses of amphotericin B were administered sequentially after voriconazole at 24-96 h. The inhibition of the fungicidal activity of amphotericin B was voriconazole dose-dependent, but seemed to be recovered once the voriconazole concentration fell below the MIC. The fungicidal activity was quickly regained after the removal of voriconazole, irrespective of the duration of voriconazole pre-exposure. ### conclusions voriconazole inhibited the fungicidal effect of sequentially administered amphotericin B in a concentration- and time-dependent manner; the clinical significance of this needs further investigation.

https://pubmed.ncbi.nlm.nih.gov/18408237/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Characterization of the inhibitory effect of voriconazole on the fungicidal activity of amphotericin B against Candida albicans in an in vitro kinetic model. The aim of the present investigation was to study and characterize the effect of voriconazole on the fungicidal activity of amphotericin B. ### methods Four strains of Candida albicans susceptible to voriconazole were exposed to voriconazole and amphotericin B, either alone, simultaneously or sequentially in an in vitro kinetic model. Bolus doses resulting in voriconazole and amphotericin B concentrations of 0.005-5 and 2.5 mg/L, respectively, were administered. Antifungal-containing RPMI 1640 was eliminated and replaced by a fresh medium using a peristaltic pump, with a flow rate adjusted to obtain the desired half-lives. With two drugs tested, a computer-controlled dosing pump compensated for differences in the elimination rates. Using static time-kill methodology, one C. albicans strain was exposed to 5 mg/L voriconazole for varying durations followed by 2.5 mg/L amphotericin B after three repeated washes of voriconazole. ### results voriconazole and amphotericin B treatment alone resulted in fungistatic and fungicidal activities, respectively. Simultaneous administration of voriconazole and amphotericin B resulted in fungicidal activity, whereas only fungistatic activity was observed when repeated doses of amphotericin B were administered sequentially after voriconazole at 24-96 h. The inhibition of the fungicidal activity of amphotericin B was voriconazole dose-dependent, but seemed to be recovered once the voriconazole concentration fell below the MIC. The fungicidal activity was quickly regained after the removal of voriconazole, irrespective of the duration of voriconazole pre-exposure. ### conclusions voriconazole inhibited the fungicidal effect of sequentially administered amphotericin B in a concentration- and time-dependent manner; the clinical significance of this needs further investigation. ### Response: voriconazole, amphotericin, B.

f9f7d99cac5550bbc464785cf3e3db64

Dual Therapy with Aspirin and Cilostazol May Improve Platelet Aggregation in Noncardioembolic Stroke Patients : A Pilot Study .

Dual Therapy with Aspirin and Cilostazol May Improve Platelet Aggregation in Noncardioembolic Stroke Patients : A Pilot Study . Objective Some previous studies have found clinical benefit of dual antiplatelet therapy with aspirin and cilostazol for prevention of secondary stroke, but the physiological mechanism involved remains unknown. We aimed to clarify the effects of aspirin/cilostazol therapy on the platelet and endothelial functions of patients with acute noncardioembolic ischemic stroke, in comparison to patients who were treated with aspirin alone. Methods The present randomized prospective pilot study enrolled 24 patients within a week after the onset of noncardioembolic ischemic stroke. The patients were randomly allocated to receive aspirin (100 mg/day) (A group; 11 patients) or cilostazol (200 mg/day) plus aspirin (100 mg/day) (CA group; 13 patients). We measured platelet aggregation, platelet activation, and the thrombomodulin (TM), highly sensitive C-reactive protein (hs-CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand (vWF) antigen levels and vWF activity over a 4-week period after enrollment. Results There was no significant difference in the platelet functions of the A and CA groups. However, the platelet aggregation induced by adenosine diphosphate (ADP) was decreased at 2 and 4 weeks (p<0.05) after treatment in comparison to the pre-treatment values in the CA group, but not in the A group. Platelet activation, and the hs-CRP, TM, ICAM-1, VCAM-1 and vWF values did not significantly decrease after treatment in either group. Conclusion Although there were no significant differences in platelet aggregation, platelet activation or the endothelial biomarker levels of the A and CA groups, dual therapy with aspirin and cilostazol inhibited platelet aggregation in comparison to the pre-treatment values, similarly to patients who received aspirin alone. This may suggest the clinical usefulness of dual therapy with aspirin and cilostazol in the treatment of patients with noncardioembolic ischemic stroke.

https://pubmed.ncbi.nlm.nih.gov/28566591/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Dual Therapy with Aspirin and Cilostazol May Improve Platelet Aggregation in Noncardioembolic Stroke Patients : A Pilot Study . Objective Some previous studies have found clinical benefit of dual antiplatelet therapy with aspirin and cilostazol for prevention of secondary stroke, but the physiological mechanism involved remains unknown. We aimed to clarify the effects of aspirin/cilostazol therapy on the platelet and endothelial functions of patients with acute noncardioembolic ischemic stroke, in comparison to patients who were treated with aspirin alone. Methods The present randomized prospective pilot study enrolled 24 patients within a week after the onset of noncardioembolic ischemic stroke. The patients were randomly allocated to receive aspirin (100 mg/day) (A group; 11 patients) or cilostazol (200 mg/day) plus aspirin (100 mg/day) (CA group; 13 patients). We measured platelet aggregation, platelet activation, and the thrombomodulin (TM), highly sensitive C-reactive protein (hs-CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand (vWF) antigen levels and vWF activity over a 4-week period after enrollment. Results There was no significant difference in the platelet functions of the A and CA groups. However, the platelet aggregation induced by adenosine diphosphate (ADP) was decreased at 2 and 4 weeks (p<0.05) after treatment in comparison to the pre-treatment values in the CA group, but not in the A group. Platelet activation, and the hs-CRP, TM, ICAM-1, VCAM-1 and vWF values did not significantly decrease after treatment in either group. Conclusion Although there were no significant differences in platelet aggregation, platelet activation or the endothelial biomarker levels of the A and CA groups, dual therapy with aspirin and cilostazol inhibited platelet aggregation in comparison to the pre-treatment values, similarly to patients who received aspirin alone. This may suggest the clinical usefulness of dual therapy with aspirin and cilostazol in the treatment of patients with noncardioembolic ischemic stroke. ### Response: Aspirin, Cilostazol

d9bc9e760dfd975a2703bfd8e7ef700e

Gemcitabine and vinorelbine have shown activity in the first-line setting .

Gemcitabine and vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma. pemetrexed-cisplatin chemotherapy is the standard of care in the first-line treatment of unresectable malignant pleural mesothelioma (MPM). Second-line cytotoxic therapy is considered for a growing group of patients, but the optimal treatment has not been defined to date. Gemcitabine and vinorelbine have shown activity in the first-line setting . The objective of this study was to evaluate the activity and toxicity of the gemcitabine-vinorelbine combination in pemetrexed-pretreated patients with MPM. ### methods From January 2004 to September 2006, 30 consecutive patients who were pretreated with pemetrexed with or without a platinum-derivative were enrolled. gemcitabine 1000 mg/m(2) and vinorelbine 25 mg/m(2) were administered intravenously on Days 1 and 8 every 3 weeks. Treatment was repeated for a maximum of 6 cycles or until progression or unacceptable toxicity. ### results A partial response was observed in 3 patients (10%; 95% confidence interval [CI], 2.1-26.5%), and 10 patients (33.3%; 95% CI, 17.3-52.8%) had stable disease after treatment. Overall, 13 patients (43.3%; 95% CI, 25.5-62.6%) achieved disease control. The median time to progression was 2.8 months (range, 0.6-12.1 months), and the median survival was 10.9 months (range, 0.8-25.3 months). Hematologic toxicity was acceptable, with grade 3 or 4 neutropenia occurring in 11% of patients and thrombocytopenia occurring in 4% of patients; no case of febrile neutropenia was observed. Nonhematologic toxicity generally was mild. ### conclusions The gemcitabine and vinorelbine combination was moderately active and had an acceptable toxicity profile in pemetrexed-pretreated patients with MPM. The role of second-line treatment in MPM needs to be evaluated in prospective trials in large series of patients who are stratified according to previous treatment and prognostic factors.

https://pubmed.ncbi.nlm.nih.gov/18286536/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Gemcitabine and vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma. pemetrexed-cisplatin chemotherapy is the standard of care in the first-line treatment of unresectable malignant pleural mesothelioma (MPM). Second-line cytotoxic therapy is considered for a growing group of patients, but the optimal treatment has not been defined to date. Gemcitabine and vinorelbine have shown activity in the first-line setting . The objective of this study was to evaluate the activity and toxicity of the gemcitabine-vinorelbine combination in pemetrexed-pretreated patients with MPM. ### methods From January 2004 to September 2006, 30 consecutive patients who were pretreated with pemetrexed with or without a platinum-derivative were enrolled. gemcitabine 1000 mg/m(2) and vinorelbine 25 mg/m(2) were administered intravenously on Days 1 and 8 every 3 weeks. Treatment was repeated for a maximum of 6 cycles or until progression or unacceptable toxicity. ### results A partial response was observed in 3 patients (10%; 95% confidence interval [CI], 2.1-26.5%), and 10 patients (33.3%; 95% CI, 17.3-52.8%) had stable disease after treatment. Overall, 13 patients (43.3%; 95% CI, 25.5-62.6%) achieved disease control. The median time to progression was 2.8 months (range, 0.6-12.1 months), and the median survival was 10.9 months (range, 0.8-25.3 months). Hematologic toxicity was acceptable, with grade 3 or 4 neutropenia occurring in 11% of patients and thrombocytopenia occurring in 4% of patients; no case of febrile neutropenia was observed. Nonhematologic toxicity generally was mild. ### conclusions The gemcitabine and vinorelbine combination was moderately active and had an acceptable toxicity profile in pemetrexed-pretreated patients with MPM. The role of second-line treatment in MPM needs to be evaluated in prospective trials in large series of patients who are stratified according to previous treatment and prognostic factors. ### Response: Gemcitabine, vinorelbine

4dfb347a107d0cb265cbec52dc05280d

The combination of tenofovir disoproxil fumarate ( TDF ) plus emtricitabine ( FTC ) is used extensively to treat HIV infection and also has potent activity against hepatitis B virus ( HBV ) infection .

Efficacy and tolerance of a combination of tenofovir disoproxil fumarate plus emtricitabine in patients with chronic hepatitis B: a European multicenter study. The combination of tenofovir disoproxil fumarate ( TDF ) plus emtricitabine ( FTC ) is used extensively to treat HIV infection and also has potent activity against hepatitis B virus ( HBV ) infection . The aim of this study was to assess the efficacy and tolerance of TDF + FTC in patients with chronic hepatitis B (CHB). ### methods Seventy eight consecutive CHB patients from five European centers were included. All started a TDF + FTC combination between October 2005 and March 2010. Virological, biochemical, and clinical data were recorded during follow-up. Tolerance was also monitored. Patients were classified into either treatment simplification (TS), where efficacy of the previous treatment was obtained at TDF + FTC initiation, and treatment intensification (TI), where the previous line of therapy had failed. ### results TDF + FTC was given as a TI to 54 patients (69%) and as a TS to 24 (31%). Among patients with TI, 83% were males. The median baseline HBV-DNA was 4.4 log10 IU/mL, and median alanine-transaminase (ALT) was 1.10 × ULN. Sixty percent were HBeAg positive, 47% had significant fibrosis (≥ F3 Metavir equivalent), and 29% had confirmed cirrhosis. Median treatment duration was 76 weeks (interquartile range 60-116). Kaplan-Meier analysis showed that, 48 weeks after TI, the probability of being HBV-DNA becoming undetectable was 76%, and reached 94% at week 96. No viral breakthrough occurred. Patients with TS (87% males, median baseline HBV-DNA 1.1 log10 IU/mL, median ALT 0.79 × ULN, 33% HBeAg positive, 61% with significant fibrosis) were treated for a median duration of 76 weeks. In this subgroup, all patients but one remained HBV-DNA undetectable and no ALT flare-up occurred during follow-up. Creatinine levels did not show kidney-function deterioration in either group of patients. ### conclusions After a median follow-up of > 76 weeks, the TDF + FTC combination showed encouraging antiviral efficacy and a good safety profile in all patients with CHB. TDF + FTC may represent an interesting clinical option to simplify therapy and increase the barrier to resistance, which should be assessed in the long term.

https://pubmed.ncbi.nlm.nih.gov/21767570/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Efficacy and tolerance of a combination of tenofovir disoproxil fumarate plus emtricitabine in patients with chronic hepatitis B: a European multicenter study. The combination of tenofovir disoproxil fumarate ( TDF ) plus emtricitabine ( FTC ) is used extensively to treat HIV infection and also has potent activity against hepatitis B virus ( HBV ) infection . The aim of this study was to assess the efficacy and tolerance of TDF + FTC in patients with chronic hepatitis B (CHB). ### methods Seventy eight consecutive CHB patients from five European centers were included. All started a TDF + FTC combination between October 2005 and March 2010. Virological, biochemical, and clinical data were recorded during follow-up. Tolerance was also monitored. Patients were classified into either treatment simplification (TS), where efficacy of the previous treatment was obtained at TDF + FTC initiation, and treatment intensification (TI), where the previous line of therapy had failed. ### results TDF + FTC was given as a TI to 54 patients (69%) and as a TS to 24 (31%). Among patients with TI, 83% were males. The median baseline HBV-DNA was 4.4 log10 IU/mL, and median alanine-transaminase (ALT) was 1.10 × ULN. Sixty percent were HBeAg positive, 47% had significant fibrosis (≥ F3 Metavir equivalent), and 29% had confirmed cirrhosis. Median treatment duration was 76 weeks (interquartile range 60-116). Kaplan-Meier analysis showed that, 48 weeks after TI, the probability of being HBV-DNA becoming undetectable was 76%, and reached 94% at week 96. No viral breakthrough occurred. Patients with TS (87% males, median baseline HBV-DNA 1.1 log10 IU/mL, median ALT 0.79 × ULN, 33% HBeAg positive, 61% with significant fibrosis) were treated for a median duration of 76 weeks. In this subgroup, all patients but one remained HBV-DNA undetectable and no ALT flare-up occurred during follow-up. Creatinine levels did not show kidney-function deterioration in either group of patients. ### conclusions After a median follow-up of > 76 weeks, the TDF + FTC combination showed encouraging antiviral efficacy and a good safety profile in all patients with CHB. TDF + FTC may represent an interesting clinical option to simplify therapy and increase the barrier to resistance, which should be assessed in the long term. ### Response: tenofovir disoproxil fumarate, emtricitabine

c9947a148118a7c7c0374ef9e7f3a915

HRQOL was better in Japanese postmenopausal women treated with tamoxifen than those treated with exemestane or anastrozole .

Health-related quality of life, psychological distress, and adverse events in postmenopausal women with breast cancer who receive tamoxifen, exemestane, or anastrozole as adjuvant endocrine therapy: National Surgical Adjuvant Study of Breast Cancer 04 (N-SAS BC 04). Health-related quality of life (HRQOL), symptoms of depression, and adverse events (AEs) were compared between Japanese postmenopausal patients with hormone-sensitive breast cancer (BC) who received adjuvant tamoxifen, exemestane, or anastrozole in an open-labeled, randomized, multicenter trial designated as the National Surgical Adjuvant Study of Breast Cancer (N-SAS BC) 04 substudy of the tamoxifen exemestane Adjuvant Multinational (TEAM) trial. During the first year of treatment, HRQOL and symptoms of depression were analyzed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and its Endocrine Symptom Subscale (ES), and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. In addition, predefined AEs were analyzed. A total of 166 eligible patients were randomly assigned to receive adjuvant tamoxifen, exemestane, or anastrozole. FACT-B scores increased after treatment began and remained significantly higher in the tamoxifen group than in the exemestane group or anastrozole group during the first year (P = 0.045). FACT-B scores were similar in the exemestane group and anastrozole group. ES scores and CES-D scores were similar in all treatment groups. Arthralgia and fatigue were less frequent, but vaginal discharge was more frequent in the tamoxifen group than in the exemestane group or anastrozole group. HRQOL was better in Japanese postmenopausal women treated with tamoxifen than those treated with exemestane or anastrozole . HRQOL and AEs were similar with exemestane and anastrozole. Given the results of the TEAM trial, upfront use of tamoxifen followed by an aromatase inhibitor (AI) may be an important option for adjuvant endocrine therapy in Japanese postmenopausal women.

https://pubmed.ncbi.nlm.nih.gov/22234519/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Health-related quality of life, psychological distress, and adverse events in postmenopausal women with breast cancer who receive tamoxifen, exemestane, or anastrozole as adjuvant endocrine therapy: National Surgical Adjuvant Study of Breast Cancer 04 (N-SAS BC 04). Health-related quality of life (HRQOL), symptoms of depression, and adverse events (AEs) were compared between Japanese postmenopausal patients with hormone-sensitive breast cancer (BC) who received adjuvant tamoxifen, exemestane, or anastrozole in an open-labeled, randomized, multicenter trial designated as the National Surgical Adjuvant Study of Breast Cancer (N-SAS BC) 04 substudy of the tamoxifen exemestane Adjuvant Multinational (TEAM) trial. During the first year of treatment, HRQOL and symptoms of depression were analyzed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and its Endocrine Symptom Subscale (ES), and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. In addition, predefined AEs were analyzed. A total of 166 eligible patients were randomly assigned to receive adjuvant tamoxifen, exemestane, or anastrozole. FACT-B scores increased after treatment began and remained significantly higher in the tamoxifen group than in the exemestane group or anastrozole group during the first year (P = 0.045). FACT-B scores were similar in the exemestane group and anastrozole group. ES scores and CES-D scores were similar in all treatment groups. Arthralgia and fatigue were less frequent, but vaginal discharge was more frequent in the tamoxifen group than in the exemestane group or anastrozole group. HRQOL was better in Japanese postmenopausal women treated with tamoxifen than those treated with exemestane or anastrozole . HRQOL and AEs were similar with exemestane and anastrozole. Given the results of the TEAM trial, upfront use of tamoxifen followed by an aromatase inhibitor (AI) may be an important option for adjuvant endocrine therapy in Japanese postmenopausal women. ### Response: tamoxifen, exemestane, anastrozole

250ab0e4ff2d5694d10eb236713fe562

This was driven by the relative advantage of weight loss compared with rosiglitazone , glimepiride , and insulin glargine , and administration frequency compared with exenatide .

Willingness to pay for diabetes drug therapy in type 2 diabetes patients: based on LEAD clinical programme results. The purpose of this study was to investigate the preferences of people with diabetes for liraglutide vs other glucose lowering drugs, based on outcomes of clinical trials. ### methods Willingness to pay (WTP) for diabetes drug treatment was assessed by combining results from a recent WTP study with analysis of results from the liraglutide Effect and Action in Diabetes (LEAD) programme. The LEAD programme included six randomised clinical trials with 3967 participants analysing efficacy and safety of liraglutide 1.2 mg (LEAD 1-6 trials), rosiglitazone (LEAD 1 trial), glimepiride (LEAD 2-3 trials), insulin glargine (LEAD 5 trial), and exenatide (LEAD 6 trial). The WTP survey used discrete choice experimental (DCE) methodology to evaluate the convenience and clinical effects of glucose lowering treatments. ### results People with type 2 diabetes were prepared to pay an extra €2.64/day for liraglutide compared with rosiglitazone, an extra €1.94/day compared with glimepiride, an extra €3.36/day compared with insulin glargine, and an extra €0.81/day compared with exenatide. Weight loss was the largest component of WTP for liraglutide compared with rosiglitazone, glimepiride, and insulin glargine. Differences in the administration of the two drugs was the largest component of WTP for liraglutide (once daily anytime) compared with exenatide (twice daily with meals). A limitation of the study was that it was based on six clinical trials where liraglutide was the test drug, but each trial had a different comparator, therefore the clinical effects of liraglutide were much better documented than the comparators. ### conclusions WTP analyses of the clinical results from the LEAD programme suggested that participants with type 2 diabetes were willing to pay appreciably more for liraglutide than other glucose lowering treatments. This was driven by the relative advantage of weight loss compared with rosiglitazone , glimepiride , and insulin glargine , and administration frequency compared with exenatide .

https://pubmed.ncbi.nlm.nih.gov/22853443/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Willingness to pay for diabetes drug therapy in type 2 diabetes patients: based on LEAD clinical programme results. The purpose of this study was to investigate the preferences of people with diabetes for liraglutide vs other glucose lowering drugs, based on outcomes of clinical trials. ### methods Willingness to pay (WTP) for diabetes drug treatment was assessed by combining results from a recent WTP study with analysis of results from the liraglutide Effect and Action in Diabetes (LEAD) programme. The LEAD programme included six randomised clinical trials with 3967 participants analysing efficacy and safety of liraglutide 1.2 mg (LEAD 1-6 trials), rosiglitazone (LEAD 1 trial), glimepiride (LEAD 2-3 trials), insulin glargine (LEAD 5 trial), and exenatide (LEAD 6 trial). The WTP survey used discrete choice experimental (DCE) methodology to evaluate the convenience and clinical effects of glucose lowering treatments. ### results People with type 2 diabetes were prepared to pay an extra €2.64/day for liraglutide compared with rosiglitazone, an extra €1.94/day compared with glimepiride, an extra €3.36/day compared with insulin glargine, and an extra €0.81/day compared with exenatide. Weight loss was the largest component of WTP for liraglutide compared with rosiglitazone, glimepiride, and insulin glargine. Differences in the administration of the two drugs was the largest component of WTP for liraglutide (once daily anytime) compared with exenatide (twice daily with meals). A limitation of the study was that it was based on six clinical trials where liraglutide was the test drug, but each trial had a different comparator, therefore the clinical effects of liraglutide were much better documented than the comparators. ### conclusions WTP analyses of the clinical results from the LEAD programme suggested that participants with type 2 diabetes were willing to pay appreciably more for liraglutide than other glucose lowering treatments. This was driven by the relative advantage of weight loss compared with rosiglitazone , glimepiride , and insulin glargine , and administration frequency compared with exenatide . ### Response: rosiglitazone, glimepiride

8cc636e27faf0c1e91489ed1d054c255

Pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as primary chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer : results of the phase II CAPRICE study .

Pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as primary chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer : results of the phase II CAPRICE study . Anthracycline and taxane-based primary chemotherapy (PCT) is the standard treatment for high-risk breast cancer (HRBC). However, conventional anthracyclines are not commonly used in elderly patients or those prone to cardiotoxicity. Pegylated liposomal doxorubicin, (PLD) has comparable efficacy, but less cardiotoxicity than conventional anthracyclines. We conducted a phase II single-arm trial to assess the efficacy and safety of PCT based on PLD followed by paclitaxel (PTX) in a HRBC population usually undertreated. Fifty patients with stage II-IIIB breast cancer and at least one risk factor for developing cardiotoxicity initiated PLD 35 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 4 weeks for four cycles, followed by 80 mg/m(2) weekly PTX for 12. Close cardiac monitoring was performed. Primary endpoint was the pathological complete response rate (pCR) in the breast. Treatment delivery and toxicities were assessed. Eighty-four per cent of patients were older than 65 years, 64 % suffered from hypertension, and 10 % had prior cardiac disease. In an intention-to-treat analysis, breast pCR was 32 % (95 % CI 19.5-46.7 %) and pCR in breast and axilla was 24 % (95 % CI 12.1-35.8 %). At diagnosis only, 26 % of patients were candidates for breast conservative surgery, which increased to 58.7 % after PCT. No significant decrease in left ventricular ejection fraction was seen. PLD followed by PTX was feasible in a fragile population of patients who were not candidates for conventional doxorubicin. Moreover, it achieved a pCR similar to standard therapy and could therefore be an option for elderly patients or cardiotoxicity-prone who present HRBC.

https://pubmed.ncbi.nlm.nih.gov/25981896/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as primary chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer : results of the phase II CAPRICE study . Anthracycline and taxane-based primary chemotherapy (PCT) is the standard treatment for high-risk breast cancer (HRBC). However, conventional anthracyclines are not commonly used in elderly patients or those prone to cardiotoxicity. Pegylated liposomal doxorubicin, (PLD) has comparable efficacy, but less cardiotoxicity than conventional anthracyclines. We conducted a phase II single-arm trial to assess the efficacy and safety of PCT based on PLD followed by paclitaxel (PTX) in a HRBC population usually undertreated. Fifty patients with stage II-IIIB breast cancer and at least one risk factor for developing cardiotoxicity initiated PLD 35 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 4 weeks for four cycles, followed by 80 mg/m(2) weekly PTX for 12. Close cardiac monitoring was performed. Primary endpoint was the pathological complete response rate (pCR) in the breast. Treatment delivery and toxicities were assessed. Eighty-four per cent of patients were older than 65 years, 64 % suffered from hypertension, and 10 % had prior cardiac disease. In an intention-to-treat analysis, breast pCR was 32 % (95 % CI 19.5-46.7 %) and pCR in breast and axilla was 24 % (95 % CI 12.1-35.8 %). At diagnosis only, 26 % of patients were candidates for breast conservative surgery, which increased to 58.7 % after PCT. No significant decrease in left ventricular ejection fraction was seen. PLD followed by PTX was feasible in a fragile population of patients who were not candidates for conventional doxorubicin. Moreover, it achieved a pCR similar to standard therapy and could therefore be an option for elderly patients or cardiotoxicity-prone who present HRBC. ### Response: doxorubicin, cyclophosphamide, paclitaxel

e062362953dea1901bad45908e5e5566

We randomly assigned 410 women with advanced ovarian cancer and residual masses larger than 1 cm after initial surgery to receive cisplatin ( 75 mg per square meter of body-surface area ) with either cyclophosphamide ( 750 mg per square meter ) or paclitaxel ( 135 mg per square meter over 24 hours ) .

Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. Chemotherapy combinations that include an alkylating agent and a platinum coordination complex have high response rates in women with advanced ovarian cancer. Such combinations provide long-term control of disease in few patients, however. We compared two combinations, cisplatin and cyclophosphamide and cisplatin and paclitaxel, in women with ovarian cancer. ### methods We randomly assigned 410 women with advanced ovarian cancer and residual masses larger than 1 cm after initial surgery to receive cisplatin ( 75 mg per square meter of body-surface area ) with either cyclophosphamide ( 750 mg per square meter ) or paclitaxel ( 135 mg per square meter over 24 hours ) . ### results Three hundred eighty-six women met all the eligibility criteria. Known prognostic factors were similar in the two treatment groups. Alopecia, neutropenia, fever, and allergic reactions were reported more frequently in the cisplatin-paclitaxel group. Among 216 women with measurable disease, 73 percent in the cisplatin-paclitaxel group responded to therapy, as compared with 60 percent in the cisplatin-cyclophosphamide group (P = 0.01). The frequency of surgically verified complete response was similar in the two groups. Progression-free survival was significantly longer (P < 0.001) in the cisplatin-paclitaxel group than in the cisplatin-cyclophosphamide group (median, 18 vs. 13 months). Survival was also significantly longer (P < 0.001) in the cisplatin-paclitaxel group (median, 38 vs. 24 months). ### conclusions Incorporating paclitaxel into first-line therapy improves the duration of progression-free survival and of overall survival in women with incompletely resected stage III and stage IV ovarian cancer.

https://pubmed.ncbi.nlm.nih.gov/7494563/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. Chemotherapy combinations that include an alkylating agent and a platinum coordination complex have high response rates in women with advanced ovarian cancer. Such combinations provide long-term control of disease in few patients, however. We compared two combinations, cisplatin and cyclophosphamide and cisplatin and paclitaxel, in women with ovarian cancer. ### methods We randomly assigned 410 women with advanced ovarian cancer and residual masses larger than 1 cm after initial surgery to receive cisplatin ( 75 mg per square meter of body-surface area ) with either cyclophosphamide ( 750 mg per square meter ) or paclitaxel ( 135 mg per square meter over 24 hours ) . ### results Three hundred eighty-six women met all the eligibility criteria. Known prognostic factors were similar in the two treatment groups. Alopecia, neutropenia, fever, and allergic reactions were reported more frequently in the cisplatin-paclitaxel group. Among 216 women with measurable disease, 73 percent in the cisplatin-paclitaxel group responded to therapy, as compared with 60 percent in the cisplatin-cyclophosphamide group (P = 0.01). The frequency of surgically verified complete response was similar in the two groups. Progression-free survival was significantly longer (P < 0.001) in the cisplatin-paclitaxel group than in the cisplatin-cyclophosphamide group (median, 18 vs. 13 months). Survival was also significantly longer (P < 0.001) in the cisplatin-paclitaxel group (median, 38 vs. 24 months). ### conclusions Incorporating paclitaxel into first-line therapy improves the duration of progression-free survival and of overall survival in women with incompletely resected stage III and stage IV ovarian cancer. ### Response: cisplatin, cyclophosphamide, paclitaxel

fa7f8a42646dfc70fb18482ae0847d68

Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men .

Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men . This study evaluates changes in cholesterol balance in hypercholesterolemic subjects following treatment with an inhibitor of cholesterol absorption or cholesterol synthesis or coadministration of both agents. This was a randomized, double blind, placebo-controlled, four-period crossover study to evaluate the effects of coadministering 10 mg ezetimibe with 20 mg simvastatin (ezetimibe/simvastatin) on cholesterol absorption and synthesis relative to either drug alone or placebo in 41 subjects. Each treatment period lasted 7 weeks. ezetimibe and ezetimibe/simvastatin decreased fractional cholesterol absorption by 65% and 59%, respectively (P < 0.001 for both relative to placebo). simvastatin did not significantly affect cholesterol absorption. ezetimibe and ezetimibe/simvastatin increased fecal sterol excretion (corrected for dietary cholesterol), which also represents net steady state cholesterol synthesis, by 109% and 79%, respectively (P < 0.001). ezetimibe, simvastatin, and ezetimibe/simvastatin decreased plasma LDL-cholesterol by 20, 38, and 55%, respectively. The coadministered therapy was well tolerated. The decreases in net cholesterol synthesis and increased fecal sterol excretion yielded nearly additive reductions in LDL-cholesterol for the coadministration of ezetimibe and simvastatin.

https://pubmed.ncbi.nlm.nih.gov/19380898/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men . This study evaluates changes in cholesterol balance in hypercholesterolemic subjects following treatment with an inhibitor of cholesterol absorption or cholesterol synthesis or coadministration of both agents. This was a randomized, double blind, placebo-controlled, four-period crossover study to evaluate the effects of coadministering 10 mg ezetimibe with 20 mg simvastatin (ezetimibe/simvastatin) on cholesterol absorption and synthesis relative to either drug alone or placebo in 41 subjects. Each treatment period lasted 7 weeks. ezetimibe and ezetimibe/simvastatin decreased fractional cholesterol absorption by 65% and 59%, respectively (P < 0.001 for both relative to placebo). simvastatin did not significantly affect cholesterol absorption. ezetimibe and ezetimibe/simvastatin increased fecal sterol excretion (corrected for dietary cholesterol), which also represents net steady state cholesterol synthesis, by 109% and 79%, respectively (P < 0.001). ezetimibe, simvastatin, and ezetimibe/simvastatin decreased plasma LDL-cholesterol by 20, 38, and 55%, respectively. The coadministered therapy was well tolerated. The decreases in net cholesterol synthesis and increased fecal sterol excretion yielded nearly additive reductions in LDL-cholesterol for the coadministration of ezetimibe and simvastatin. ### Response: ezetimibe, simvastatin

7f084f3d889b6776bd35615a619ad87c

The US government regulated precursor chemicals , ephedrine and pseudoephedrine , multiple times to limit methamphetamine production/availability and thus methamphetamine problems .

Impacts of federal precursor chemical regulations on methamphetamine arrests. The US government regulated precursor chemicals , ephedrine and pseudoephedrine , multiple times to limit methamphetamine production/availability and thus methamphetamine problems . Research has found that the regulations reduced methamphetamine hospital admissions, but authors have argued that other problems were unaffected. This study examines whether the regulations impacted methamphetamine arrests. ### design ARIMA-intervention time-series analysis with control series. ### setting California (1982-2001). ### measurements Dependent variable series: monthly methamphetamine arrests. Control series: monthly marijuana arrests and cocaine/heroin arrests. ### interventions Bulk powder ephedrine and pseudoephedrine: regulated November 1989. Products containing ephedrine as the single active medicinal ingredient: regulated August 1995. pseudoephedrine products: regulated October 1997. Large-scale producers used ephedrine and pseudoephedrine in these forms. Ephedrine combined with other active medicinal ingredients (e.g. various cold medicines)-used mainly by small-scale producers: regulated October 1996. ### findings The regulation targeting small-scale producers (1996) had no significant impact. In contrast, methamphetamine arrests stopped rising and dropped 31% to 45% each of the three times precursor chemicals used by large-scale producers were regulated. Within 3 years of the bulk powder regulation (1989) and again within 2 years of the ephedrine single ingredient regulation (1995), arrests fully rebounded. During the 4 years following the last regulation (pseudoephedrine products, 1997) arrests only partially rebounded. These effects parallel those reported on hospital admissions. The control series were generally unaffected. ### conclusions Precursor regulations targeting large-scale producers impacted methamphetamine arrests, a criminal justice problem, much as they impacted the public health problem of methamphetamine hospital admissions. Ongoing research is needed to determine whether these problems eventually fully rebound from the last regulation.

https://pubmed.ncbi.nlm.nih.gov/15784062/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Impacts of federal precursor chemical regulations on methamphetamine arrests. The US government regulated precursor chemicals , ephedrine and pseudoephedrine , multiple times to limit methamphetamine production/availability and thus methamphetamine problems . Research has found that the regulations reduced methamphetamine hospital admissions, but authors have argued that other problems were unaffected. This study examines whether the regulations impacted methamphetamine arrests. ### design ARIMA-intervention time-series analysis with control series. ### setting California (1982-2001). ### measurements Dependent variable series: monthly methamphetamine arrests. Control series: monthly marijuana arrests and cocaine/heroin arrests. ### interventions Bulk powder ephedrine and pseudoephedrine: regulated November 1989. Products containing ephedrine as the single active medicinal ingredient: regulated August 1995. pseudoephedrine products: regulated October 1997. Large-scale producers used ephedrine and pseudoephedrine in these forms. Ephedrine combined with other active medicinal ingredients (e.g. various cold medicines)-used mainly by small-scale producers: regulated October 1996. ### findings The regulation targeting small-scale producers (1996) had no significant impact. In contrast, methamphetamine arrests stopped rising and dropped 31% to 45% each of the three times precursor chemicals used by large-scale producers were regulated. Within 3 years of the bulk powder regulation (1989) and again within 2 years of the ephedrine single ingredient regulation (1995), arrests fully rebounded. During the 4 years following the last regulation (pseudoephedrine products, 1997) arrests only partially rebounded. These effects parallel those reported on hospital admissions. The control series were generally unaffected. ### conclusions Precursor regulations targeting large-scale producers impacted methamphetamine arrests, a criminal justice problem, much as they impacted the public health problem of methamphetamine hospital admissions. Ongoing research is needed to determine whether these problems eventually fully rebound from the last regulation. ### Response: pseudoephedrine, methamphetamine, methamphetamine

967ea702edc061a8a1b8b17a2d779d8c

We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine , lomustine , and vincristine ( PCV ) chemotherapy to radiotherapy ( RT ) .

Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. Anaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine , lomustine , and vincristine ( PCV ) chemotherapy to radiotherapy ( RT ) . ### Patients And Methods Adult patients with newly diagnosed anaplastic oligodendroglial tumors were randomly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV. An exploratory analysis of the correlation between 1p/19q status and survival was part of the study. Retrospectively, the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase (IDH) gene were determined. The primary end points were overall survival (OS) and progression-free survival based on intent-to-treat analysis. ### results A total of 368 patients were enrolled. With a median follow-up of 140 months, OS in the RT/PCV arm was significantly longer (42.3 v 30.6 months in the RT arm, hazard ratio [HR], 0.75; 95% CI, 0.60 to 0.95). In the 80 patients with a 1p/19q codeletion, OS was increased, with a trend toward more benefit from adjuvant PCV (OS not reached in the RT/PCV group v 112 months in the RT group; HR, 0.56; 95% CI, 0.31 to 1.03). IDH mutational status was also of prognostic significance. ### conclusion The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors. 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non-1p/19q-deleted tumors.

https://pubmed.ncbi.nlm.nih.gov/23071237/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. Anaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine , lomustine , and vincristine ( PCV ) chemotherapy to radiotherapy ( RT ) . ### Patients And Methods Adult patients with newly diagnosed anaplastic oligodendroglial tumors were randomly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV. An exploratory analysis of the correlation between 1p/19q status and survival was part of the study. Retrospectively, the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase (IDH) gene were determined. The primary end points were overall survival (OS) and progression-free survival based on intent-to-treat analysis. ### results A total of 368 patients were enrolled. With a median follow-up of 140 months, OS in the RT/PCV arm was significantly longer (42.3 v 30.6 months in the RT arm, hazard ratio [HR], 0.75; 95% CI, 0.60 to 0.95). In the 80 patients with a 1p/19q codeletion, OS was increased, with a trend toward more benefit from adjuvant PCV (OS not reached in the RT/PCV group v 112 months in the RT group; HR, 0.56; 95% CI, 0.31 to 1.03). IDH mutational status was also of prognostic significance. ### conclusion The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors. 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non-1p/19q-deleted tumors. ### Response: procarbazine, lomustine, vincristine, radiotherapy

8c229f9bee992965dc0cac147088ce6d

A phase II clinical trial was conducted to evaluate the efficacy and toxicity of vinorelbine plus gemcitabine in very old patients with inoperable ( stage IIIb or IV ) NSCLC .

A phase II trial of vinorelbine plus gemcitabine in previously untreated inoperable (stage IIIb/IV) non-small-cell lung cancer patients aged 80 or older. vinorelbine and gemcitabine are two active single agents with mild toxicity profiles that are used in the treatment of non-small-cell lung cancer (NSCLC). Whether or not very old NSCLC patients, such as those aged 80 years or older, should still be considered for chemotherapy is unknown, since their response to the treatment is also unknown. A phase II clinical trial was conducted to evaluate the efficacy and toxicity of vinorelbine plus gemcitabine in very old patients with inoperable ( stage IIIb or IV ) NSCLC . vinorelbine 20 mg/m(2) was given as a 10-min intravenous infusion, followed by a 30-min intravenous infusion of gemcitabine 800 mg/m(2) on days 1, 8, and 15 of each 28-day cycle. From March 1998 to December 2001, 20 patients (16 males, four females) were enrolled in the study. The median age was 83 years, within the range 80-88 years. The median number of treatment cycles per patient was four. With the exception of one, all patients received at least two cycles of treatment. Thirteen patients achieved a partial response, with an overall response rate of 65% (95% confidence interval, 44.1-85.9%). Median survival was 10 months. The significant (WHO grade 3/4) toxicities were myelosuppression, including leukopenia in five (25%) patients, neutropenia in eight (40%), anaemia in six (30%), and thrombocytopenia in three (15%) patients. Febrile neutropenia occurred in two patients and accounted for one treatment-related death. Non-haematological toxicity was generally mild, except one patient who suffered from grade 3 interstitial pneumonitis. Another patient suffered from a cerebral infarction after three cycles of treatment. In conclusion, the combination of vinorelbine and gemcitabine in very old patients with advanced NSCLC is a highly active regimen with an acceptable toxicity profile.

https://pubmed.ncbi.nlm.nih.gov/12711125/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: A phase II trial of vinorelbine plus gemcitabine in previously untreated inoperable (stage IIIb/IV) non-small-cell lung cancer patients aged 80 or older. vinorelbine and gemcitabine are two active single agents with mild toxicity profiles that are used in the treatment of non-small-cell lung cancer (NSCLC). Whether or not very old NSCLC patients, such as those aged 80 years or older, should still be considered for chemotherapy is unknown, since their response to the treatment is also unknown. A phase II clinical trial was conducted to evaluate the efficacy and toxicity of vinorelbine plus gemcitabine in very old patients with inoperable ( stage IIIb or IV ) NSCLC . vinorelbine 20 mg/m(2) was given as a 10-min intravenous infusion, followed by a 30-min intravenous infusion of gemcitabine 800 mg/m(2) on days 1, 8, and 15 of each 28-day cycle. From March 1998 to December 2001, 20 patients (16 males, four females) were enrolled in the study. The median age was 83 years, within the range 80-88 years. The median number of treatment cycles per patient was four. With the exception of one, all patients received at least two cycles of treatment. Thirteen patients achieved a partial response, with an overall response rate of 65% (95% confidence interval, 44.1-85.9%). Median survival was 10 months. The significant (WHO grade 3/4) toxicities were myelosuppression, including leukopenia in five (25%) patients, neutropenia in eight (40%), anaemia in six (30%), and thrombocytopenia in three (15%) patients. Febrile neutropenia occurred in two patients and accounted for one treatment-related death. Non-haematological toxicity was generally mild, except one patient who suffered from grade 3 interstitial pneumonitis. Another patient suffered from a cerebral infarction after three cycles of treatment. In conclusion, the combination of vinorelbine and gemcitabine in very old patients with advanced NSCLC is a highly active regimen with an acceptable toxicity profile. ### Response: vinorelbine, gemcitabine

e49b2723397411ce15b49761296e1576

Tobramycin was probably less effective than gentamicin in combination with the penicillinase-resistant penicillins against enterococci .

Comparative in vitro activity of nafcillin, oxacillin, and methicillin in combination with gentamicin and tobramycin against enterococci. The in vitro activity of nafcillin, oxacillin, and methicillin alone and in combination with gentamicin and tobramycin against 30 strains of enterococci was investigated. The penicillinase-resistant penicillins were less active than penicillin and ampicillin against the enterococci. nafcillin was more active than oxacillin and methicillin. Sixty-six percent of strains were inhibited by nafcillin at 6.25 mug/ml, but none was inhibited by oxacillin and methicillin at the same concentration. At 12.5 mug/ml, 83, 16, and 0% were inhibited by nafcillin, oxacillin, and methicillin, respectively. By using a variety of criteria and analyses, it was shown that none of the antibiotic combinations studied demonstrated enhanced killing of all strains of enterococci. nafcillin-gentamicin was the best combination, and enhanced killing was demonstrated against most strains. oxacillin was more effective than methicillin when combined with gentamicin. Tobramycin was probably less effective than gentamicin in combination with the penicillinase-resistant penicillins against enterococci .

https://pubmed.ncbi.nlm.nih.gov/836017/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Comparative in vitro activity of nafcillin, oxacillin, and methicillin in combination with gentamicin and tobramycin against enterococci. The in vitro activity of nafcillin, oxacillin, and methicillin alone and in combination with gentamicin and tobramycin against 30 strains of enterococci was investigated. The penicillinase-resistant penicillins were less active than penicillin and ampicillin against the enterococci. nafcillin was more active than oxacillin and methicillin. Sixty-six percent of strains were inhibited by nafcillin at 6.25 mug/ml, but none was inhibited by oxacillin and methicillin at the same concentration. At 12.5 mug/ml, 83, 16, and 0% were inhibited by nafcillin, oxacillin, and methicillin, respectively. By using a variety of criteria and analyses, it was shown that none of the antibiotic combinations studied demonstrated enhanced killing of all strains of enterococci. nafcillin-gentamicin was the best combination, and enhanced killing was demonstrated against most strains. oxacillin was more effective than methicillin when combined with gentamicin. Tobramycin was probably less effective than gentamicin in combination with the penicillinase-resistant penicillins against enterococci . ### Response: Tobramycin, gentamicin, penicillins

aca79bc0aba0854bf6e69d6468578862

Despite the absence of strong data , entecavir and telbivudine seem to be the preferred options for nucleoside analogue-naive CHB patients with chronic kidney disease , depending on viraemia and severity of renal dysfunction .

Review article: nucleos(t)ide analogues in patients with chronic hepatitis B virus infection and chronic kidney disease. The treatment of chronic hepatitis B (CHB) in patients with chronic kidney disease (CKD) is based on nucleoside (lamivudine, telbivudine, entecavir) or nucleotide (adefovir, tenofovir) analogues (NAs), but it may be complex and the information is scarce. entecavir and tenofovir represent the currently recommended first-line NAs for NA-naive CHB patients, while tenofovir is the NA of choice for CHB patients with resistance to nucleosides. ### aim To review the efficacy and safety of NAs in adult CHB patients with CKD and to provide reasonable recommendations for their optimal management. ### methods Literature search in PubMed/Medline and manual search of relevant articles, reviews and book chapters. ### results NAs are cleared by kidneys and their dosage should be adjusted in patients with creatinine clearance <50 mL/min. There are concerns about nephrotoxic potential of the nucleotides, particularly adefovir, while improvements of creatinine clearance have been reported under telbivudine. Most existing data in CHB patients with CKD are for lamivudine and, less frequently, for other NAs, mostly entecavir. Besides CHB, NA should be used in case of immunosuppressive therapy in any HBsAg-positive patient with CKD including renal transplant (RT) recipients and in anti-HBs-positive recipients of kidney grafts from HBsAg-positive donors. ### conclusions Chronic hepatitis B patients with chronic kidney disease receiving nucleoside analogues should be followed carefully for treatment efficacy and renal safety. Despite the absence of strong data , entecavir and telbivudine seem to be the preferred options for nucleoside analogue-naive CHB patients with chronic kidney disease , depending on viraemia and severity of renal dysfunction . More studies are certainly needed in this setting.

https://pubmed.ncbi.nlm.nih.gov/24299322/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Review article: nucleos(t)ide analogues in patients with chronic hepatitis B virus infection and chronic kidney disease. The treatment of chronic hepatitis B (CHB) in patients with chronic kidney disease (CKD) is based on nucleoside (lamivudine, telbivudine, entecavir) or nucleotide (adefovir, tenofovir) analogues (NAs), but it may be complex and the information is scarce. entecavir and tenofovir represent the currently recommended first-line NAs for NA-naive CHB patients, while tenofovir is the NA of choice for CHB patients with resistance to nucleosides. ### aim To review the efficacy and safety of NAs in adult CHB patients with CKD and to provide reasonable recommendations for their optimal management. ### methods Literature search in PubMed/Medline and manual search of relevant articles, reviews and book chapters. ### results NAs are cleared by kidneys and their dosage should be adjusted in patients with creatinine clearance <50 mL/min. There are concerns about nephrotoxic potential of the nucleotides, particularly adefovir, while improvements of creatinine clearance have been reported under telbivudine. Most existing data in CHB patients with CKD are for lamivudine and, less frequently, for other NAs, mostly entecavir. Besides CHB, NA should be used in case of immunosuppressive therapy in any HBsAg-positive patient with CKD including renal transplant (RT) recipients and in anti-HBs-positive recipients of kidney grafts from HBsAg-positive donors. ### conclusions Chronic hepatitis B patients with chronic kidney disease receiving nucleoside analogues should be followed carefully for treatment efficacy and renal safety. Despite the absence of strong data , entecavir and telbivudine seem to be the preferred options for nucleoside analogue-naive CHB patients with chronic kidney disease , depending on viraemia and severity of renal dysfunction . More studies are certainly needed in this setting. ### Response: entecavir, telbivudine

bddb579070955f889fea255e42d919f5

Results from clinical trials evaluating agents such as ixabepilone , albumin-bound paclitaxel , capecitabine , vinorelbine , pemetrexed , and irinotecan are presented .

Management of metastatic breast cancer: monotherapy options for patients resistant to anthracyclines and taxanes. Resistance to chemotherapeutic agents is a significant obstacle to the effective treatment of metastatic breast cancer (MBC). Anthracycline- and taxane-based regimens are active as first-line treatment for MBC; however, MBC often progresses because of primary or acquired resistance to anthracyclines and taxanes. There are few options for the treatment of patients with anthracycline- and taxane-resistant or taxane-refractory MBC. This article reviews several single agents that have demonstrated activity as treatment for patients with MBC who progress during, or rapidly following, treatment with anthracyclines and taxanes. Results from clinical trials evaluating agents such as ixabepilone , albumin-bound paclitaxel , capecitabine , vinorelbine , pemetrexed , and irinotecan are presented . Single-agent capecitabine is approved for the treatment of patients after failure of anthracyclines and taxanes. ixabepilone has demonstrated efficacy in patients with MBC resistant to multiple chemotherapeutic agents and is the only agent approved by the Food and Drug Administration as monotherapy for anthracycline-, taxane-, and capecitabine-resistant MBC. Improved treatment strategies and further evaluation of newer agents may reduce the current burden of treatment-resistant or treatment-refractory MBC.

https://pubmed.ncbi.nlm.nih.gov/19675449/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Management of metastatic breast cancer: monotherapy options for patients resistant to anthracyclines and taxanes. Resistance to chemotherapeutic agents is a significant obstacle to the effective treatment of metastatic breast cancer (MBC). Anthracycline- and taxane-based regimens are active as first-line treatment for MBC; however, MBC often progresses because of primary or acquired resistance to anthracyclines and taxanes. There are few options for the treatment of patients with anthracycline- and taxane-resistant or taxane-refractory MBC. This article reviews several single agents that have demonstrated activity as treatment for patients with MBC who progress during, or rapidly following, treatment with anthracyclines and taxanes. Results from clinical trials evaluating agents such as ixabepilone , albumin-bound paclitaxel , capecitabine , vinorelbine , pemetrexed , and irinotecan are presented . Single-agent capecitabine is approved for the treatment of patients after failure of anthracyclines and taxanes. ixabepilone has demonstrated efficacy in patients with MBC resistant to multiple chemotherapeutic agents and is the only agent approved by the Food and Drug Administration as monotherapy for anthracycline-, taxane-, and capecitabine-resistant MBC. Improved treatment strategies and further evaluation of newer agents may reduce the current burden of treatment-resistant or treatment-refractory MBC. ### Response: ixabepilone, paclitaxel, capecitabine, vinorelbine, pemetrexed, irinotecan

1a4b7002c34da6a84d3592bc7bc47325

The clinical studies provide evidence that combined fluticasone/formoterol is more efficacious than fluticasone or formoterol given alone , and provides similar improvements in lung function to fluticasone ( Flixotide ( ® ) ) and formoterol ( Foradil ( ® ) ) administered concurrently .

[A new fixed dose combination of fluticasone and formoterol in a pressurised metered-dose inhaler for the treatment of asthma]. The combination of an inhaled corticosteroid and a long acting beta-2 agonist is indicated for the regular treatment of persistent moderate-to-severe asthmatics whose asthma is not controlled by inhaled corticosteroids and the occasional use of a short acting beta-2 agonist. The aim of this review is to give an overview of the rationale of combining formoterol and fluticasone and to analyze the clinical data concerning a new fixed combination of fluticasone and formoterol in a pressurised metered-dose inhaler with a dose counter (Flutiform(®)) that was approved for the treatment of asthma in France in 2013. The clinical studies provide evidence that combined fluticasone/formoterol is more efficacious than fluticasone or formoterol given alone , and provides similar improvements in lung function to fluticasone ( Flixotide ( ® ) ) and formoterol ( Foradil ( ® ) ) administered concurrently . The combination of fluticasone/formoterol gave a more rapid bronchodilatation than the combination fluticasone/salmeterol. As a whole, the combination of fluticasone/formoterol had similar efficacy and tolerability profiles to the combinations of either budesonide/formoterol or fluticasone/salmeterol.

https://pubmed.ncbi.nlm.nih.gov/25391505/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: [A new fixed dose combination of fluticasone and formoterol in a pressurised metered-dose inhaler for the treatment of asthma]. The combination of an inhaled corticosteroid and a long acting beta-2 agonist is indicated for the regular treatment of persistent moderate-to-severe asthmatics whose asthma is not controlled by inhaled corticosteroids and the occasional use of a short acting beta-2 agonist. The aim of this review is to give an overview of the rationale of combining formoterol and fluticasone and to analyze the clinical data concerning a new fixed combination of fluticasone and formoterol in a pressurised metered-dose inhaler with a dose counter (Flutiform(®)) that was approved for the treatment of asthma in France in 2013. The clinical studies provide evidence that combined fluticasone/formoterol is more efficacious than fluticasone or formoterol given alone , and provides similar improvements in lung function to fluticasone ( Flixotide ( ® ) ) and formoterol ( Foradil ( ® ) ) administered concurrently . The combination of fluticasone/formoterol gave a more rapid bronchodilatation than the combination fluticasone/salmeterol. As a whole, the combination of fluticasone/formoterol had similar efficacy and tolerability profiles to the combinations of either budesonide/formoterol or fluticasone/salmeterol. ### Response: fluticasone, formoterol, fluticasone, formoterol

b34f763241f46b224f71b6494c6b2fb8

Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen : a TransATAC study .

Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen : a TransATAC study . PURPOSE To determine whether the Recurrence Score (RS) provided independent information on risk of distant recurrence (DR) in the tamoxifen and anastrozole arms of the Arimidex, tamoxifen, Alone or in Combination (ATAC) Trial. PATIENTS AND METHODS RNA was extracted from 1,372 tumor blocks from postmenopausal patients with hormone receptor-positive primary breast cancer in the monotherapy arms of ATAC. Twenty-one genes were assessed by quantitative reverse transcriptase polymerase chain reaction, and the RS was calculated. Cox proportional hazards models assessed the value of adding RS to a model with clinical variables (age, tumor size, grade, and treatment) in node-negative (N0) and node-positive (N+) women. RESULTS Reportable scores were available from 1,231 evaluable patients (N0, n = 872; N+, n = 306; and node status unknown, n = 53); 72, 74, and six DRs occurred in N0, N+, and node status unknown patients, respectively. For both N0 and N+ patients, RS was significantly associated with time to DR in multivariate analyses (P < .001 for N0 and P = .002 for N+). RS also showed significant prognostic value beyond that provided by Adjuvant! Online (P < .001). Nine-year DR rates in low (RS < 18), intermediate (RS = 18 to 30), and high RS (RS > or = 31) groups were 4%, 12%, and 25%, respectively, in N0 patients and 17%, 28%, and 49%, respectively, in N+ patients. The prognostic value of RS was similar in anastrozole- and tamoxifen-treated patients. CONCLUSION This study confirmed the performance of RS in postmenopausal HR+ patients treated with tamoxifen in a large contemporary population and demonstrated that RS is an independent predictor of DR in N0 and N+ hormone receptor-positive patients treated with anastrozole, adding value to estimates with standard clinicopathologic features.

https://pubmed.ncbi.nlm.nih.gov/20212256/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen : a TransATAC study . PURPOSE To determine whether the Recurrence Score (RS) provided independent information on risk of distant recurrence (DR) in the tamoxifen and anastrozole arms of the Arimidex, tamoxifen, Alone or in Combination (ATAC) Trial. PATIENTS AND METHODS RNA was extracted from 1,372 tumor blocks from postmenopausal patients with hormone receptor-positive primary breast cancer in the monotherapy arms of ATAC. Twenty-one genes were assessed by quantitative reverse transcriptase polymerase chain reaction, and the RS was calculated. Cox proportional hazards models assessed the value of adding RS to a model with clinical variables (age, tumor size, grade, and treatment) in node-negative (N0) and node-positive (N+) women. RESULTS Reportable scores were available from 1,231 evaluable patients (N0, n = 872; N+, n = 306; and node status unknown, n = 53); 72, 74, and six DRs occurred in N0, N+, and node status unknown patients, respectively. For both N0 and N+ patients, RS was significantly associated with time to DR in multivariate analyses (P < .001 for N0 and P = .002 for N+). RS also showed significant prognostic value beyond that provided by Adjuvant! Online (P < .001). Nine-year DR rates in low (RS < 18), intermediate (RS = 18 to 30), and high RS (RS > or = 31) groups were 4%, 12%, and 25%, respectively, in N0 patients and 17%, 28%, and 49%, respectively, in N+ patients. The prognostic value of RS was similar in anastrozole- and tamoxifen-treated patients. CONCLUSION This study confirmed the performance of RS in postmenopausal HR+ patients treated with tamoxifen in a large contemporary population and demonstrated that RS is an independent predictor of DR in N0 and N+ hormone receptor-positive patients treated with anastrozole, adding value to estimates with standard clinicopathologic features. ### Response: anastrozole, tamoxifen

a8312c2cee1d08090d323d2c0b611d9e

When novel DMARDs were used as monotherapies , greater ACR20/50/70 responses were observed with tocilizumab than with anti-tumor necrosis factor agents ( aTNF ) or tofacitinib .

Comparative Efficacy of Novel DMARDs as Monotherapy and in Combination with Methotrexate in Rheumatoid Arthritis Patients with Inadequate Response to Conventional DMARDs: A Network Meta-Analysis. Given the availability of a number of alternative biologic treatment options and other novel disease-modifying antirheumatic drugs (DMARDs) for the treatment of patients with rheumatoid arthritis (RA), clinicians are faced with an increasingly challenging choice regarding optimal treatment. Biologics are usually combined with traditional DMARDs, primarily methotrexate (MTX), but some biologics and tofacitinib (together referred to in this article as novel DMARDs) have been shown to be efficacious as monotherapy as well. In real-world practice, approximately one-third of RA patients receiving biologics are on monotherapy, primarily because of intolerance of, or noncompliance with, MTX. Limited data, however, are available analyzing the effectiveness of monotherapy compared with combination therapy across novel DMARDs. ### objective To compare American College of Rheumatology (ACR) responses to approved novel DMARDs used as monotherapy or as combination therapy with methotrexate (MTX) at 24 weeks in RA patients who have shown inadequate response to conventional DMARDs (DMARD-IR). ### methods Through a systematic review of the literature, we identified randomized controlled trials that assessed approved novel DMARDs used as monotherapy or as combination therapy with MTX in DMARD-IR RA patients. Twenty-eight RCTs were identified that evaluated abatacept, anakinra, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, tocilizumab, or tofacitinib. ACR responses at 24 weeks were extracted and combined by means of Bayesian network meta-analyses. ### results With the exception of anakinra plus MTX, which was less efficacious, most novel DMARDs, when used in combination with MTX, demonstrated comparable ACR responses. When novel DMARDs were used as monotherapies , greater ACR20/50/70 responses were observed with tocilizumab than with anti-tumor necrosis factor agents ( aTNF ) or tofacitinib . Furthermore, ACR20/50/70 responses with tocilizumab plus MTX were similar to those with tocilizumab monotherapy (odds ratio [OR] for the indirect comparison = 1.08, 95% credible interval [CrI] = 0.40-2.84; OR = 1.24, CrI = 0.44-3.61; OR = 0.95, CrI = 0.33-2.72, respectively), whereas greater responses were observed with aTNF plus MTX than with aTNF monotherapy (OR = 2.41, CrI = 0.51-11.61; OR = 2.85, CrI = 0.51-17.67; OR = 1.28, CrI = 0.21-8.42, respectively). Relative efficacy estimates for the indirect comparison of tofacitinib plus MTX with tofacitinib monotherapy were very uncertain. ### conclusions Results suggest that in combination with MTX most of the available novel DMARDs have similar levels of efficacy in DMARD-IR patients. As monotherapy, however, tocilizumab displayed higher ACR responses than aTNF or tofacitinib. ACR responses with tocilizumab plus MTX were similar to those with tocilizumab as monotherapy, whereas aTNF in combination with MTX demonstrated greater ACR responses than aTNF as monotherapy.

https://pubmed.ncbi.nlm.nih.gov/25943002/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Comparative Efficacy of Novel DMARDs as Monotherapy and in Combination with Methotrexate in Rheumatoid Arthritis Patients with Inadequate Response to Conventional DMARDs: A Network Meta-Analysis. Given the availability of a number of alternative biologic treatment options and other novel disease-modifying antirheumatic drugs (DMARDs) for the treatment of patients with rheumatoid arthritis (RA), clinicians are faced with an increasingly challenging choice regarding optimal treatment. Biologics are usually combined with traditional DMARDs, primarily methotrexate (MTX), but some biologics and tofacitinib (together referred to in this article as novel DMARDs) have been shown to be efficacious as monotherapy as well. In real-world practice, approximately one-third of RA patients receiving biologics are on monotherapy, primarily because of intolerance of, or noncompliance with, MTX. Limited data, however, are available analyzing the effectiveness of monotherapy compared with combination therapy across novel DMARDs. ### objective To compare American College of Rheumatology (ACR) responses to approved novel DMARDs used as monotherapy or as combination therapy with methotrexate (MTX) at 24 weeks in RA patients who have shown inadequate response to conventional DMARDs (DMARD-IR). ### methods Through a systematic review of the literature, we identified randomized controlled trials that assessed approved novel DMARDs used as monotherapy or as combination therapy with MTX in DMARD-IR RA patients. Twenty-eight RCTs were identified that evaluated abatacept, anakinra, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, tocilizumab, or tofacitinib. ACR responses at 24 weeks were extracted and combined by means of Bayesian network meta-analyses. ### results With the exception of anakinra plus MTX, which was less efficacious, most novel DMARDs, when used in combination with MTX, demonstrated comparable ACR responses. When novel DMARDs were used as monotherapies , greater ACR20/50/70 responses were observed with tocilizumab than with anti-tumor necrosis factor agents ( aTNF ) or tofacitinib . Furthermore, ACR20/50/70 responses with tocilizumab plus MTX were similar to those with tocilizumab monotherapy (odds ratio [OR] for the indirect comparison = 1.08, 95% credible interval [CrI] = 0.40-2.84; OR = 1.24, CrI = 0.44-3.61; OR = 0.95, CrI = 0.33-2.72, respectively), whereas greater responses were observed with aTNF plus MTX than with aTNF monotherapy (OR = 2.41, CrI = 0.51-11.61; OR = 2.85, CrI = 0.51-17.67; OR = 1.28, CrI = 0.21-8.42, respectively). Relative efficacy estimates for the indirect comparison of tofacitinib plus MTX with tofacitinib monotherapy were very uncertain. ### conclusions Results suggest that in combination with MTX most of the available novel DMARDs have similar levels of efficacy in DMARD-IR patients. As monotherapy, however, tocilizumab displayed higher ACR responses than aTNF or tofacitinib. ACR responses with tocilizumab plus MTX were similar to those with tocilizumab as monotherapy, whereas aTNF in combination with MTX demonstrated greater ACR responses than aTNF as monotherapy. ### Response: tocilizumab, tofacitinib

f084f9073c5c11b6bcc521f746c7f0f8

Paclitaxel showed synergistic anti-proliferative impacts with fulvestrant .

Anti-tumor efficacy of fulvestrant in estrogen receptor positive gastric cancer. To investigate the prognostic role of the estrogen receptor (ER) in gastric cancer (GC) patients, tumor tissues from 932 patients with advanced GC were assessed for ER expression using immunohistochemistry, and their clinicopathologic features were evaluated. Forty patients (4.3%) had ER expression and they were more frequently associated with diffuse type gastric cancer and shorter disease free survival. Furthermore, we carried out in vitro analysis to evaluate the effect of ER modulation on the proliferation of GC cell lines. Estradiol enhanced proliferation of ER positive GC cells while it did not show any effect on ER negative GC cells. When ER was inhibited by fulvestrant and ER siRNA, estradiol-induced proliferation of ER positive GC cell was suppressed. Paclitaxel showed synergistic anti-proliferative impacts with fulvestrant . Suppressing ER by fulvestrant, paclitaxel and ER siRNA showed increased expression of E-cadherin, which is a crucial factor in diffuse-type carcinogenesis.

https://pubmed.ncbi.nlm.nih.gov/25534230/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Anti-tumor efficacy of fulvestrant in estrogen receptor positive gastric cancer. To investigate the prognostic role of the estrogen receptor (ER) in gastric cancer (GC) patients, tumor tissues from 932 patients with advanced GC were assessed for ER expression using immunohistochemistry, and their clinicopathologic features were evaluated. Forty patients (4.3%) had ER expression and they were more frequently associated with diffuse type gastric cancer and shorter disease free survival. Furthermore, we carried out in vitro analysis to evaluate the effect of ER modulation on the proliferation of GC cell lines. Estradiol enhanced proliferation of ER positive GC cells while it did not show any effect on ER negative GC cells. When ER was inhibited by fulvestrant and ER siRNA, estradiol-induced proliferation of ER positive GC cell was suppressed. Paclitaxel showed synergistic anti-proliferative impacts with fulvestrant . Suppressing ER by fulvestrant, paclitaxel and ER siRNA showed increased expression of E-cadherin, which is a crucial factor in diffuse-type carcinogenesis. ### Response: Paclitaxel, fulvestrant

0702354a47fff4da19d07a1467671915

The experimental protocol was as follows : ( 1 ) at time zero , intravenous infusion of ritodrine was begun ; ( 2 ) at 120 min , 2 % lidocaine was given epidurally to achieve a sensory level of at least T6 ; and ( 3 ) at 135 min , an intravenous bolus of either ephedrine , phenylephrine , or normal saline-control was given , followed by a continuous intravenous infusion of the same agent for 30 min .

Ephedrine remains the vasopressor of choice for treatment of hypotension during ritodrine infusion and epidural anesthesia. Historically, ephedrine has been the vasopressor of choice for treatment of most cases of hypotension in obstetric patients. However, the choice of vasopressor in the parturient receiving a beta-adrenergic agent for tocolysis has not been evaluated extensively. The current study evaluated whether ephedrine or phenylephrine better restores uterine blood flow and fetal oxygenation during ritodrine infusion and epidural anesthesia-induced hypotension in gravid ewes. ### methods Fourteen chronically instrumented gravid ewes between 0.8 and 0.9 timed gestational age were used. On separate days, each animal underwent the experimental protocol with one of three agents: ephedrine, phenylephrine, and normal saline-control. The experimental protocol was as follows : ( 1 ) at time zero , intravenous infusion of ritodrine was begun ; ( 2 ) at 120 min , 2 % lidocaine was given epidurally to achieve a sensory level of at least T6 ; and ( 3 ) at 135 min , an intravenous bolus of either ephedrine , phenylephrine , or normal saline-control was given , followed by a continuous intravenous infusion of the same agent for 30 min . In the ephedrine and phenylephrine experiments, the rate of infusion was adjusted to maintain maternal mean arterial pressure close to baseline. ### results ritodrine infusion alone significantly increased maternal heart rate and cardiac output in all three groups. Epidural anesthesia during ritodrine infusion significantly decreased maternal mean arterial pressure, heart rate, cardiac output, uterine blood flow, and fetal arterial oxygen tension for each of the three groups. Both ephedrine and phenylephrine restored maternal mean arterial pressure to baseline, as designed. Ephedrine significantly increased uterine blood flow and fetal arterial oxygen tension when compared with normal saline--control, but phenylephrine did not. phenylephrine significantly increased uterine vascular resistance when compared with normal saline--control, but ephedrine did not. ### conclusions Although ephedrine and phenylephrine provided similar restoration of maternal mean arterial pressure, ephedrine was superior to phenylephrine in restoring uterine blood flow during ritodrine infusion and epidural anesthesia-induced hypotension in gravid ewes. Also, ephedrine, but not phenylephrine, significantly improved fetal oxygenation, when compared to normal saline--control.

https://pubmed.ncbi.nlm.nih.gov/8017645/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Ephedrine remains the vasopressor of choice for treatment of hypotension during ritodrine infusion and epidural anesthesia. Historically, ephedrine has been the vasopressor of choice for treatment of most cases of hypotension in obstetric patients. However, the choice of vasopressor in the parturient receiving a beta-adrenergic agent for tocolysis has not been evaluated extensively. The current study evaluated whether ephedrine or phenylephrine better restores uterine blood flow and fetal oxygenation during ritodrine infusion and epidural anesthesia-induced hypotension in gravid ewes. ### methods Fourteen chronically instrumented gravid ewes between 0.8 and 0.9 timed gestational age were used. On separate days, each animal underwent the experimental protocol with one of three agents: ephedrine, phenylephrine, and normal saline-control. The experimental protocol was as follows : ( 1 ) at time zero , intravenous infusion of ritodrine was begun ; ( 2 ) at 120 min , 2 % lidocaine was given epidurally to achieve a sensory level of at least T6 ; and ( 3 ) at 135 min , an intravenous bolus of either ephedrine , phenylephrine , or normal saline-control was given , followed by a continuous intravenous infusion of the same agent for 30 min . In the ephedrine and phenylephrine experiments, the rate of infusion was adjusted to maintain maternal mean arterial pressure close to baseline. ### results ritodrine infusion alone significantly increased maternal heart rate and cardiac output in all three groups. Epidural anesthesia during ritodrine infusion significantly decreased maternal mean arterial pressure, heart rate, cardiac output, uterine blood flow, and fetal arterial oxygen tension for each of the three groups. Both ephedrine and phenylephrine restored maternal mean arterial pressure to baseline, as designed. Ephedrine significantly increased uterine blood flow and fetal arterial oxygen tension when compared with normal saline--control, but phenylephrine did not. phenylephrine significantly increased uterine vascular resistance when compared with normal saline--control, but ephedrine did not. ### conclusions Although ephedrine and phenylephrine provided similar restoration of maternal mean arterial pressure, ephedrine was superior to phenylephrine in restoring uterine blood flow during ritodrine infusion and epidural anesthesia-induced hypotension in gravid ewes. Also, ephedrine, but not phenylephrine, significantly improved fetal oxygenation, when compared to normal saline--control. ### Response: ritodrine, lidocaine, phenylephrine, ephedrine

f9b1f1a93c415dc0e29c0a8bed13dc1c

compared to busulfan and cyclophosphamide as conditioning regimen for allogeneic stem cell transplant from matched siblings and unrelated donors for acute myeloid leukemia .

compared to busulfan and cyclophosphamide as conditioning regimen for allogeneic stem cell transplant from matched siblings and unrelated donors for acute myeloid leukemia . busulfan plus cyclophosphamide (BuCy) is the traditional conditioning regimen for allogeneic stem cell transplant (allo-SCT) for young, fit patients with acute myeloid leukemia (AML). The thiotepa-busulfan-fludarabine (TBF) protocol has recently demonstrated promising outcome in cord blood and haploidentical SCT; however, there is limited evidence about this regimen in transplant from matched siblings (MSD) and unrelated donors (UD). We retrospectively compared outcomes of 2523 patients aged 18-50 with AML in remission, undergoing transplant from MSD or UD prepared with either TBF or BuCy conditioning. A 1:3 pair-matched analysis was performed: 146 patients receiving TBF were compared with 438 patients receiving BuCy. Relapse risk was significantly lower in the TBF when compared with BuCy group (HR 0.6, P = .02), while NRM did not differ. No significant difference was observed in LFS and OS between the two regimens. TBF was associated with a trend towards higher risk of grades III-IV aGVHD (HR 1.8, P = .06) and inferior cGVHD (HR 0.7, P = .04) when compared with BuCy. In patients undergoing transplant in first remission, the advantage for TBF in terms of relapse was more evident (HR 0.4, P = .02), leading to a trend for better LFS in favor of TBF (HR 0.7, P = .10), while OS did not differ between the two cohorts. In conclusion, TBF represents a valid myeloablative conditioning regimen providing significantly lower relapse and similar survival when compared with BuCy. Patients in first remission appear to gain the most from this protocol, as in this subgroup a tendency for better LFS was observed when compared with BuCy.

https://pubmed.ncbi.nlm.nih.gov/30033639/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: compared to busulfan and cyclophosphamide as conditioning regimen for allogeneic stem cell transplant from matched siblings and unrelated donors for acute myeloid leukemia . busulfan plus cyclophosphamide (BuCy) is the traditional conditioning regimen for allogeneic stem cell transplant (allo-SCT) for young, fit patients with acute myeloid leukemia (AML). The thiotepa-busulfan-fludarabine (TBF) protocol has recently demonstrated promising outcome in cord blood and haploidentical SCT; however, there is limited evidence about this regimen in transplant from matched siblings (MSD) and unrelated donors (UD). We retrospectively compared outcomes of 2523 patients aged 18-50 with AML in remission, undergoing transplant from MSD or UD prepared with either TBF or BuCy conditioning. A 1:3 pair-matched analysis was performed: 146 patients receiving TBF were compared with 438 patients receiving BuCy. Relapse risk was significantly lower in the TBF when compared with BuCy group (HR 0.6, P = .02), while NRM did not differ. No significant difference was observed in LFS and OS between the two regimens. TBF was associated with a trend towards higher risk of grades III-IV aGVHD (HR 1.8, P = .06) and inferior cGVHD (HR 0.7, P = .04) when compared with BuCy. In patients undergoing transplant in first remission, the advantage for TBF in terms of relapse was more evident (HR 0.4, P = .02), leading to a trend for better LFS in favor of TBF (HR 0.7, P = .10), while OS did not differ between the two cohorts. In conclusion, TBF represents a valid myeloablative conditioning regimen providing significantly lower relapse and similar survival when compared with BuCy. Patients in first remission appear to gain the most from this protocol, as in this subgroup a tendency for better LFS was observed when compared with BuCy. ### Response: busulfan, cyclophosphamide

dc747d23089de0920b9129198f64388e

Posttransplant immunosuppression to prevent graft-versus-host disease ( GVHD ) consisted of cyclosporine and prednisone ( CSA/PSE ) .

A prospective randomized comparison of total body irradiation-etoposide versus busulfan-cyclophosphamide as preparatory regimens for bone marrow transplantation in patients with leukemia who were not in first remission: a Southwest Oncology Group study. Two novel preparatory regimens for conditioning of patients with leukemia for allogeneic bone marrow transplantation (BMT) from histocompatible sibling donors have been tested in a phase III trial under the auspices of the Southwest Oncology Group (SWOG 8612). These two regimens consisted either of fractionated total body irradiation and etoposide (FTBI/VP-16) or high-dose busulfan with cyclophosphamide (BU/CY). Only patients who had failed prior conventional management at least once were study eligible, ie, no patients with acute leukemia in first remission (CR) or in first chronic phase (CP) of chronic myelogenous leukemia (CML) participated. Patients were stratified according to the following risk criteria: "good-risk" patients were those who were in second CR of their acute leukemia or in accelerated phase (AP) of CML; "poor-risk" patients had further advanced stages of leukemia. During a 52-month period, 131 patients were registered of whom 122 (93%) were study eligible. Sixty-one eligible patients were randomized to the FTBI/VP-16 arm and 61 to the BU/CY regimen. Of these 122 patients, 114 (93%) proceeded to BMT according to protocol. Posttransplant immunosuppression to prevent graft-versus-host disease ( GVHD ) consisted of cyclosporine and prednisone ( CSA/PSE ) . Neither overall survival nor disease-free survival (DFS) differed significantly between the two treatment groups (P = .89 and .69, respectively). Estimated DFS for "good-risk" patients who had been prepared with the FTBI/VP-16 regimen was 55% +/- 11%, as compared with patients treated with BU/CY whose DFS figure was 34% +/- 10% (P = .30). For "poor-risk" candidates, the DFS rates at 24 months were 17% +/- 6% (for FTBI/VP-16) and 24% +/- 8% (for BU/CY), respectively (P = .81). These figures do not differ significantly, especially in view of the fact that the "good-risk" patients prepared with the FTBI/VP-16 regimen were younger than those treated with BU/CY. Both regimens were well tolerated with no regimen-related deaths encountered during the 6-week period after BMT. This study also confirmed the efficacy of the CSA/PSE combination in the prevention of GVHD with 23 of 113 (20%) of BMT recipients developing moderate to severe acute GVHD. The leading cause for treatment failure was leukemic relapse (45 of the 114 BMT recipients suffered a recurrence of their leukemia), whereas 38 patients died without evidence of relapse. Thirty-one patients are alive and in continued CR after marrow transplantation; four are alive in relapse.(ABSTRACT TRUNCATED AT 400 WORDS)

https://pubmed.ncbi.nlm.nih.gov/8471778/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: A prospective randomized comparison of total body irradiation-etoposide versus busulfan-cyclophosphamide as preparatory regimens for bone marrow transplantation in patients with leukemia who were not in first remission: a Southwest Oncology Group study. Two novel preparatory regimens for conditioning of patients with leukemia for allogeneic bone marrow transplantation (BMT) from histocompatible sibling donors have been tested in a phase III trial under the auspices of the Southwest Oncology Group (SWOG 8612). These two regimens consisted either of fractionated total body irradiation and etoposide (FTBI/VP-16) or high-dose busulfan with cyclophosphamide (BU/CY). Only patients who had failed prior conventional management at least once were study eligible, ie, no patients with acute leukemia in first remission (CR) or in first chronic phase (CP) of chronic myelogenous leukemia (CML) participated. Patients were stratified according to the following risk criteria: "good-risk" patients were those who were in second CR of their acute leukemia or in accelerated phase (AP) of CML; "poor-risk" patients had further advanced stages of leukemia. During a 52-month period, 131 patients were registered of whom 122 (93%) were study eligible. Sixty-one eligible patients were randomized to the FTBI/VP-16 arm and 61 to the BU/CY regimen. Of these 122 patients, 114 (93%) proceeded to BMT according to protocol. Posttransplant immunosuppression to prevent graft-versus-host disease ( GVHD ) consisted of cyclosporine and prednisone ( CSA/PSE ) . Neither overall survival nor disease-free survival (DFS) differed significantly between the two treatment groups (P = .89 and .69, respectively). Estimated DFS for "good-risk" patients who had been prepared with the FTBI/VP-16 regimen was 55% +/- 11%, as compared with patients treated with BU/CY whose DFS figure was 34% +/- 10% (P = .30). For "poor-risk" candidates, the DFS rates at 24 months were 17% +/- 6% (for FTBI/VP-16) and 24% +/- 8% (for BU/CY), respectively (P = .81). These figures do not differ significantly, especially in view of the fact that the "good-risk" patients prepared with the FTBI/VP-16 regimen were younger than those treated with BU/CY. Both regimens were well tolerated with no regimen-related deaths encountered during the 6-week period after BMT. This study also confirmed the efficacy of the CSA/PSE combination in the prevention of GVHD with 23 of 113 (20%) of BMT recipients developing moderate to severe acute GVHD. The leading cause for treatment failure was leukemic relapse (45 of the 114 BMT recipients suffered a recurrence of their leukemia), whereas 38 patients died without evidence of relapse. Thirty-one patients are alive and in continued CR after marrow transplantation; four are alive in relapse.(ABSTRACT TRUNCATED AT 400 WORDS) ### Response: cyclosporine, prednisone

f76446fad47e58f6c8cbe3add6b8bde7

Tadalafil 20 mg was preferred to sildenafil 50 mg for the initiation of ED therapy in this study population .

A multicenter, randomized, double-blind, crossover study of patient preference for tadalafil 20 mg or sildenafil citrate 50 mg during initiation of treatment for erectile dysfunction. tadalafil is a phosphodiesterase 5 (PDE5) inhibitor approved in >30 countries for the treatment of erectile dysfunction (ED). It has been shown to improve erectile function compared with placebo in Phase III studies, but clinical experience comparing tadalafil with the PDE5 inhibitor sildenafil citrate is lacking. ### objective This study compared patient preference for tadalafil 20 mg or sildenafil 50 mg during initial treatment for ED. It also compared the tolerability of the 2 agents at these doses. ### methods This randomized, double-blind, fixed-dose, 2-period crossover trial took place at 13 sites in the United States and Germany. Patients were randomized 1:1 to receive 4 weeks of treatment with tadalafil 20 mg or sildenafil 50 mg, followed by the alternative treatment, to be taken as needed up to once daily before sexual activity. ### results The study enrolled 215 men with ED, 109 randomized to the tadalafil-sildenafil sequence and 106 to the sildenafil-tadalafil sequence. Their mean age was 49.8 years; 84.7% were sildenafil naive and 15.3% had undergone a previous inadequate trial of sildenafil. Most patients had moderate ED (60.5%) of >or=1 year's duration (74.9%). Of 190 evaluable patients, 126 (66.3%) preferred to initiate treatment with tadalafil, compared with 64 (33.7%) with sildenafil (P < 0.001). Patients' preference did not differ by age, duration of ED, treatment sequence, or previous sildenafil exposure. Both medications were well tolerated, with no significant differences in the incidence of treatment-emergent adverse events. Headache (11.2% tadalafil, 8.8% sildenafil), dyspepsia (6.0% and 4.2%, respectively), nasopharyngitis (4.7% and 2.8%), and flushing (2.8% and 4.7%) were the most common adverse events. The rate of ocular disturbances was low: 1 patient experienced intermittent bilateral reduction in visual acuity with tadalafil, and 2 exhibited conjunctival hyperemia or eyelid edema with sildenafil. ### conclusions Tadalafil 20 mg was preferred to sildenafil 50 mg for the initiation of ED therapy in this study population . Both medications were well tolerated.

https://pubmed.ncbi.nlm.nih.gov/14693299/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: A multicenter, randomized, double-blind, crossover study of patient preference for tadalafil 20 mg or sildenafil citrate 50 mg during initiation of treatment for erectile dysfunction. tadalafil is a phosphodiesterase 5 (PDE5) inhibitor approved in >30 countries for the treatment of erectile dysfunction (ED). It has been shown to improve erectile function compared with placebo in Phase III studies, but clinical experience comparing tadalafil with the PDE5 inhibitor sildenafil citrate is lacking. ### objective This study compared patient preference for tadalafil 20 mg or sildenafil 50 mg during initial treatment for ED. It also compared the tolerability of the 2 agents at these doses. ### methods This randomized, double-blind, fixed-dose, 2-period crossover trial took place at 13 sites in the United States and Germany. Patients were randomized 1:1 to receive 4 weeks of treatment with tadalafil 20 mg or sildenafil 50 mg, followed by the alternative treatment, to be taken as needed up to once daily before sexual activity. ### results The study enrolled 215 men with ED, 109 randomized to the tadalafil-sildenafil sequence and 106 to the sildenafil-tadalafil sequence. Their mean age was 49.8 years; 84.7% were sildenafil naive and 15.3% had undergone a previous inadequate trial of sildenafil. Most patients had moderate ED (60.5%) of >or=1 year's duration (74.9%). Of 190 evaluable patients, 126 (66.3%) preferred to initiate treatment with tadalafil, compared with 64 (33.7%) with sildenafil (P < 0.001). Patients' preference did not differ by age, duration of ED, treatment sequence, or previous sildenafil exposure. Both medications were well tolerated, with no significant differences in the incidence of treatment-emergent adverse events. Headache (11.2% tadalafil, 8.8% sildenafil), dyspepsia (6.0% and 4.2%, respectively), nasopharyngitis (4.7% and 2.8%), and flushing (2.8% and 4.7%) were the most common adverse events. The rate of ocular disturbances was low: 1 patient experienced intermittent bilateral reduction in visual acuity with tadalafil, and 2 exhibited conjunctival hyperemia or eyelid edema with sildenafil. ### conclusions Tadalafil 20 mg was preferred to sildenafil 50 mg for the initiation of ED therapy in this study population . Both medications were well tolerated. ### Response: Tadalafil, sildenafil

f445aee54445b061d12d9c0396914f89

Reactivity of factor IXa with basic pancreatic trypsin inhibitor is enhanced by low molecular weight heparin ( enoxaparin ) .

Heparin modulates the 99-loop of factor IXa: effects on reactivity with isolated Kunitz-type inhibitor domains. Reactivity of factor IXa with basic pancreatic trypsin inhibitor is enhanced by low molecular weight heparin ( enoxaparin ) . Previous studies by us have suggested that this effect involves allosteric modulation of factor IXa. We examined the reactivity of factor IXa with several isolated Kunitz-type inhibitor domains: basic pancreatic trypsin inhibitor, the Kunitz inhibitor domain of protease Nexin-2, and the first two inhibitor domains of tissue factor pathway inhibitor. We find that enhancement of factor IXa reactivity by enoxaparin is greatest for basic pancreatic trypsin inhibitor (>10-fold), followed by the second tissue factor pathway inhibitor domain (1.7-fold) and the Kunitz inhibitor domain of protease Nexin-2 (1.4-fold). Modeling studies of factor IXa with basic pancreatic trypsin inhibitor suggest that binding of this inhibitor is sterically hindered by the 99-loop of factor IXa, specifically residue Lys(98). Slow-binding kinetic studies support the formation of a weak initial enzyme-inhibitor complex between factor IXa and basic pancreatic trypsin inhibitor that is facilitated by enoxaparin binding. Mutation of Lys(98) to Ala in factor IXa results in enhanced reactivity with all inhibitors examined, whereas almost completely abrogating the enhancing effects of enoxaparin. The results implicate Lys(98) and the 99-loop of factor IXa in defining enzyme inhibitor specificity. More importantly, these results demonstrate the ability of factor IXa to be allosterically modulated by occupation of the heparin-binding exosite.

https://pubmed.ncbi.nlm.nih.gov/16766524/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Heparin modulates the 99-loop of factor IXa: effects on reactivity with isolated Kunitz-type inhibitor domains. Reactivity of factor IXa with basic pancreatic trypsin inhibitor is enhanced by low molecular weight heparin ( enoxaparin ) . Previous studies by us have suggested that this effect involves allosteric modulation of factor IXa. We examined the reactivity of factor IXa with several isolated Kunitz-type inhibitor domains: basic pancreatic trypsin inhibitor, the Kunitz inhibitor domain of protease Nexin-2, and the first two inhibitor domains of tissue factor pathway inhibitor. We find that enhancement of factor IXa reactivity by enoxaparin is greatest for basic pancreatic trypsin inhibitor (>10-fold), followed by the second tissue factor pathway inhibitor domain (1.7-fold) and the Kunitz inhibitor domain of protease Nexin-2 (1.4-fold). Modeling studies of factor IXa with basic pancreatic trypsin inhibitor suggest that binding of this inhibitor is sterically hindered by the 99-loop of factor IXa, specifically residue Lys(98). Slow-binding kinetic studies support the formation of a weak initial enzyme-inhibitor complex between factor IXa and basic pancreatic trypsin inhibitor that is facilitated by enoxaparin binding. Mutation of Lys(98) to Ala in factor IXa results in enhanced reactivity with all inhibitors examined, whereas almost completely abrogating the enhancing effects of enoxaparin. The results implicate Lys(98) and the 99-loop of factor IXa in defining enzyme inhibitor specificity. More importantly, these results demonstrate the ability of factor IXa to be allosterically modulated by occupation of the heparin-binding exosite. ### Response: heparin, enoxaparin

9f6a5691861df15334acb4b555ed7ee0

Either 5-fluorouracil ( 5-FU ) and leucovorin for 6 months or 5-FU and levamisole for 12 months are currently considered standard adjuvant treatment for stage III colorectal cancer .

National Cancer Institute Clinical Trials Program in Colorectal Cancer. Colorectal cancer will be diagnosed in approximately 150,000 patients in the USA this year. Chemotherapy has recently been shown to improve survival when given as adjuvant therapy to surgery in patients with stage III colorectal cancer. Demonstration of this benefit required large, randomized controlled trials. Either 5-fluorouracil ( 5-FU ) and leucovorin for 6 months or 5-FU and levamisole for 12 months are currently considered standard adjuvant treatment for stage III colorectal cancer . However, current adjuvant trials are comparing continuous infusion and intravenous bolus 5-FU regimens and oral uracil/Ftorafur with intravenous 5-FU and leucovorin, as well as studying the timing of chemotherapy in the adjuvant setting. Subsequent adjuvant trials will examine newer regimens with activity in advanced colorectal cancer, as well as the efficacy of monoclonal antibodies. Other trials will study which type of surgery is optimal and whether adjuvant therapy is helpful in stage II colon cancer. Trials in metastatic disease will focus on combinations of newer agents which may improve survival in this patient group. Studies in rectal cancer will focus on determining which agents are optimal in combination with radiation therapy in the adjuvant setting. Molecular characteristics of tumor cells are being defined, which may guide therapy in the future. Careful, logically designed clinical trials will hopefully provide more efficacious therapy for this common cancer.

https://pubmed.ncbi.nlm.nih.gov/9750034/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: National Cancer Institute Clinical Trials Program in Colorectal Cancer. Colorectal cancer will be diagnosed in approximately 150,000 patients in the USA this year. Chemotherapy has recently been shown to improve survival when given as adjuvant therapy to surgery in patients with stage III colorectal cancer. Demonstration of this benefit required large, randomized controlled trials. Either 5-fluorouracil ( 5-FU ) and leucovorin for 6 months or 5-FU and levamisole for 12 months are currently considered standard adjuvant treatment for stage III colorectal cancer . However, current adjuvant trials are comparing continuous infusion and intravenous bolus 5-FU regimens and oral uracil/Ftorafur with intravenous 5-FU and leucovorin, as well as studying the timing of chemotherapy in the adjuvant setting. Subsequent adjuvant trials will examine newer regimens with activity in advanced colorectal cancer, as well as the efficacy of monoclonal antibodies. Other trials will study which type of surgery is optimal and whether adjuvant therapy is helpful in stage II colon cancer. Trials in metastatic disease will focus on combinations of newer agents which may improve survival in this patient group. Studies in rectal cancer will focus on determining which agents are optimal in combination with radiation therapy in the adjuvant setting. Molecular characteristics of tumor cells are being defined, which may guide therapy in the future. Careful, logically designed clinical trials will hopefully provide more efficacious therapy for this common cancer. ### Response: leucovorin, levamisole, 5-FU, 5-FU

9303b9f861ab1f3f663f6a8f02a12cf4

Postmenopausal women with stage I-IIIA hormone receptor-positive breast cancer , who were disease-free after about 5 years of treatment with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor , were randomly assigned ( 1:1 ) to receive 5 years of letrozole ( 2·5 mg orally per day ) or placebo .

Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial. The optimal duration of extended therapy with aromatase inhibitors in patients with postmenopausal breast cancer is unknown. In the NSABP B-42 study, we aimed to determine whether extended letrozole treatment improves disease-free survival after 5 years of aromatase inhibitor-based therapy in women with postmenopausal breast cancer. ### methods This randomised, double-blind, placebo-controlled, phase 3 trial was done in 158 centres in the USA, Canada, and Ireland. Postmenopausal women with stage I-IIIA hormone receptor-positive breast cancer , who were disease-free after about 5 years of treatment with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor , were randomly assigned ( 1:1 ) to receive 5 years of letrozole ( 2·5 mg orally per day ) or placebo . Randomisation was stratified by pathological node status, previous tamoxifen use, and lowest bone mineral density T score in the lumbosacral spine, total hip, or femoral neck. The primary endpoint was disease-free survival, defined as time from randomisation to breast cancer recurrence, second primary malignancy, or death, and was analysed by intention to treat. To adjust for previous interim analyses, the two-sided statistical significance level for disease-free survival was set at 0·0418. This study is registered with ClinicalTrials.gov, number NCT00382070, is active, and is no longer enrolling patients. ### findings Between Sept 28, 2006, and Jan 6, 2010, 3966 patients were randomly assigned to receive letrozole (n=1983) or placebo (n=1983). Follow-up information was available for 3903 patients for the analyses of disease-free survival. Median follow-up was 6·9 years (IQR 6·1-7·5). letrozole treatment did not significantly improve disease-free survival (339 disease-free survival events were reported in the placebo group and 292 disease-free survival events were reported in the letrozole group; hazard ratio 0·85, 95% CI 0·73-0·999; p=0·048). 7-year disease-free survival estimate was 81·3% (95% CI 79·3-83·1) in the placebo group and 84·7% (82·9-86·4) in the letrozole group. The most common grade 3 adverse events were arthralgia (47 [2%] of 1933 patients in the placebo group vs 50 [3%] of 1941 patients in the letrozole group) and back pain (44 [2%] vs 38 [2%]). The most common grade 4 adverse event in the placebo group was thromboembolic event (eight [<1%]) and the most common grade 4 adverse events in the letrozole group were urinary tract infection, hypokalaemia, and left ventricular systolic dysfunction (four [<1%] each). ### interpretation After 5 years of aromatase inhibitor-based therapy, 5 years of letrozole therapy did not significantly prolong disease-free survival compared with placebo. Careful assessment of potential risks and benefits is required before recommending extended letrozole therapy to patients with early-stage breast cancer. ### funding National Cancer Institute, Korea Health Technology R&D Project, Novartis.

https://pubmed.ncbi.nlm.nih.gov/30509771/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial. The optimal duration of extended therapy with aromatase inhibitors in patients with postmenopausal breast cancer is unknown. In the NSABP B-42 study, we aimed to determine whether extended letrozole treatment improves disease-free survival after 5 years of aromatase inhibitor-based therapy in women with postmenopausal breast cancer. ### methods This randomised, double-blind, placebo-controlled, phase 3 trial was done in 158 centres in the USA, Canada, and Ireland. Postmenopausal women with stage I-IIIA hormone receptor-positive breast cancer , who were disease-free after about 5 years of treatment with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor , were randomly assigned ( 1:1 ) to receive 5 years of letrozole ( 2·5 mg orally per day ) or placebo . Randomisation was stratified by pathological node status, previous tamoxifen use, and lowest bone mineral density T score in the lumbosacral spine, total hip, or femoral neck. The primary endpoint was disease-free survival, defined as time from randomisation to breast cancer recurrence, second primary malignancy, or death, and was analysed by intention to treat. To adjust for previous interim analyses, the two-sided statistical significance level for disease-free survival was set at 0·0418. This study is registered with ClinicalTrials.gov, number NCT00382070, is active, and is no longer enrolling patients. ### findings Between Sept 28, 2006, and Jan 6, 2010, 3966 patients were randomly assigned to receive letrozole (n=1983) or placebo (n=1983). Follow-up information was available for 3903 patients for the analyses of disease-free survival. Median follow-up was 6·9 years (IQR 6·1-7·5). letrozole treatment did not significantly improve disease-free survival (339 disease-free survival events were reported in the placebo group and 292 disease-free survival events were reported in the letrozole group; hazard ratio 0·85, 95% CI 0·73-0·999; p=0·048). 7-year disease-free survival estimate was 81·3% (95% CI 79·3-83·1) in the placebo group and 84·7% (82·9-86·4) in the letrozole group. The most common grade 3 adverse events were arthralgia (47 [2%] of 1933 patients in the placebo group vs 50 [3%] of 1941 patients in the letrozole group) and back pain (44 [2%] vs 38 [2%]). The most common grade 4 adverse event in the placebo group was thromboembolic event (eight [<1%]) and the most common grade 4 adverse events in the letrozole group were urinary tract infection, hypokalaemia, and left ventricular systolic dysfunction (four [<1%] each). ### interpretation After 5 years of aromatase inhibitor-based therapy, 5 years of letrozole therapy did not significantly prolong disease-free survival compared with placebo. Careful assessment of potential risks and benefits is required before recommending extended letrozole therapy to patients with early-stage breast cancer. ### funding National Cancer Institute, Korea Health Technology R&D Project, Novartis. ### Response: tamoxifen, letrozole

df88c83dd24ae56c97d4410a9555cf7c

Efficacy of sorafenib combined with the pan-CDK inhibitor flavopiridol was tested both in vitro and in xenograft experiments .

Cyclin E1 Inhibition can Overcome Sorafenib Resistance in Hepatocellular Carcinoma Cells Through Mcl-1 Suppression. To clarify the effects of cyclin E1 suppression on antitumor efficacy of sorafenib in hepatocellular carcinoma cells and to explore the potential of combining sorafenib with cyclin-dependent kinase (CDK) inhibition in therapy. ### Experimental Design The effects of cyclin E1 suppression on sorafenib-induced apoptosis were tested in both sorafenib-sensitive (Huh-7 and HepG2, IC50 5-6 μmol/L) and sorafenib-resistant (Huh-7R and HepG2R, IC50 14-15 μmol/L) hepatocellular carcinoma cells. The activity of pertinent signaling pathways and the expression of cell cycle and apoptosis-related proteins were measured using Western blotting. Efficacy of sorafenib combined with the pan-CDK inhibitor flavopiridol was tested both in vitro and in xenograft experiments . The pertinent downstream mediators of antitumor efficacy were tested in transient transfection and RNA interference experiments. ### results Cyclin E1 mRNA and protein expressions were suppressed after sorafenib treatment in sorafenib-sensitive but not in sorafenib-resistant hepatocellular carcinoma cells. Changes in cyclin E2 or D1 were not correlated with sorafenib sensitivity. The knockdown of cyclin E1 expression reversed the resistance of hepatocellular carcinoma cells to sorafenib in terms of cell growth and apoptosis induction, whereas the overexpression of cyclin E1 increased the resistance to sorafenib. The growth-inhibitory and apoptosis-inducing effects of sorafenib were enhanced by flavopiridol, and Mcl-1 suppression was determined to play a critical role in mediating this enhancing effect. ### conclusions The cyclin E1 suppression in hepatocellular carcinoma cells may serve as a pharmacodynamic biomarker for predicting sorafenib efficacy. The combination of sorafenib and CDK inhibitors may improve the efficacy of sorafenib in hepatocellular carcinoma. Clin Cancer Res; 22(10); 2555-64. ©2015 AACR.

https://pubmed.ncbi.nlm.nih.gov/26603262/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Cyclin E1 Inhibition can Overcome Sorafenib Resistance in Hepatocellular Carcinoma Cells Through Mcl-1 Suppression. To clarify the effects of cyclin E1 suppression on antitumor efficacy of sorafenib in hepatocellular carcinoma cells and to explore the potential of combining sorafenib with cyclin-dependent kinase (CDK) inhibition in therapy. ### Experimental Design The effects of cyclin E1 suppression on sorafenib-induced apoptosis were tested in both sorafenib-sensitive (Huh-7 and HepG2, IC50 5-6 μmol/L) and sorafenib-resistant (Huh-7R and HepG2R, IC50 14-15 μmol/L) hepatocellular carcinoma cells. The activity of pertinent signaling pathways and the expression of cell cycle and apoptosis-related proteins were measured using Western blotting. Efficacy of sorafenib combined with the pan-CDK inhibitor flavopiridol was tested both in vitro and in xenograft experiments . The pertinent downstream mediators of antitumor efficacy were tested in transient transfection and RNA interference experiments. ### results Cyclin E1 mRNA and protein expressions were suppressed after sorafenib treatment in sorafenib-sensitive but not in sorafenib-resistant hepatocellular carcinoma cells. Changes in cyclin E2 or D1 were not correlated with sorafenib sensitivity. The knockdown of cyclin E1 expression reversed the resistance of hepatocellular carcinoma cells to sorafenib in terms of cell growth and apoptosis induction, whereas the overexpression of cyclin E1 increased the resistance to sorafenib. The growth-inhibitory and apoptosis-inducing effects of sorafenib were enhanced by flavopiridol, and Mcl-1 suppression was determined to play a critical role in mediating this enhancing effect. ### conclusions The cyclin E1 suppression in hepatocellular carcinoma cells may serve as a pharmacodynamic biomarker for predicting sorafenib efficacy. The combination of sorafenib and CDK inhibitors may improve the efficacy of sorafenib in hepatocellular carcinoma. Clin Cancer Res; 22(10); 2555-64. ©2015 AACR. ### Response: sorafenib, flavopiridol

7ac7f5459159308e28b92b4bf1bdf281

Codelivery of sorafenib and curcumin by directed self-assembled nanoparticles enhances therapeutic effect on hepatocellular carcinoma .

Codelivery of sorafenib and curcumin by directed self-assembled nanoparticles enhances therapeutic effect on hepatocellular carcinoma . Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Herein, we first reported the codelivery of sorafenib and curcumin by directed self-assembled nanoparticles (SCN) to enhance the therapeutic effect on HCC. SCN was formed by employing the hydrophobic interactions among the lipophilic structure in sorafenib, curcumin, and similar hydrophobic segments of polyethylene glycol derivative of vitamin E succinate (PEG-VES), which comprised uniform spherical particles with particle size of 84.97 ± 6.03 nm. SCN presented superior effects over sorafenib, curcumin, and their physical mixture (Sora + Cur) on enhancing in vitro cytotoxicity and cell apoptosis in BEL-7402 cells and Hep G2 cells, and antiangiogenesis activities in tube formation and microvessel formation from aortic rings. Moreover, the tissue concentration of sorafenib and curcumin in gastrointestinal tract and major organs were significantly improved after their coassembly into SCN. In particular, in BEL-7402 cells induced tumor xenograft, SCN treatment displayed the obviously enhanced inhibitory effect on tumor progression over free drug monotherapy or their physical mixture, with significantly increased antiproliferation and antiangiogenesis capability. Thereby, the codelivered nanoassemblies of sorafenib and curcumin provided a promising strategy to enhance the combinational therapy of HCC.

https://pubmed.ncbi.nlm.nih.gov/25622075/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Codelivery of sorafenib and curcumin by directed self-assembled nanoparticles enhances therapeutic effect on hepatocellular carcinoma . Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Herein, we first reported the codelivery of sorafenib and curcumin by directed self-assembled nanoparticles (SCN) to enhance the therapeutic effect on HCC. SCN was formed by employing the hydrophobic interactions among the lipophilic structure in sorafenib, curcumin, and similar hydrophobic segments of polyethylene glycol derivative of vitamin E succinate (PEG-VES), which comprised uniform spherical particles with particle size of 84.97 ± 6.03 nm. SCN presented superior effects over sorafenib, curcumin, and their physical mixture (Sora + Cur) on enhancing in vitro cytotoxicity and cell apoptosis in BEL-7402 cells and Hep G2 cells, and antiangiogenesis activities in tube formation and microvessel formation from aortic rings. Moreover, the tissue concentration of sorafenib and curcumin in gastrointestinal tract and major organs were significantly improved after their coassembly into SCN. In particular, in BEL-7402 cells induced tumor xenograft, SCN treatment displayed the obviously enhanced inhibitory effect on tumor progression over free drug monotherapy or their physical mixture, with significantly increased antiproliferation and antiangiogenesis capability. Thereby, the codelivered nanoassemblies of sorafenib and curcumin provided a promising strategy to enhance the combinational therapy of HCC. ### Response: sorafenib, curcumin

975254697195819e20dfd94a71918e9a

Single treatment of closantel plus albendazole mixture reduced egg counts in camels by 100 % , 100 % , 98 % and 77 % for Haemonchus longistipes , Ascaris spp . , Monezia expansa and Fasciola hepatica , respectively .

Efficacy of closantel plus albendazole liquid suspension against natural infection of gastrointestinal parasites in camels. Oral administration of closantel in a dose of 10 mg/kg plus albendazole in a dose of 5 mg/kg liquid suspension was studied in 75 camels naturally infected with various types of gastrointestinal parasites. The camels involved were 15 pregnant she-camels, 20 non-pregnant she-camels and 40 male camels of various ages. Each camel received a single oral dose of closantel (10 mg/kg) plus albendazole (5 mg/kg) orally. Two weeks later, 20 camels of this group were re-dosed again with the same dose of the anthelmintic. Fecal samples were collected per rectum from all camels at the time of treatment and again 14 and 42 days post treatment. Fecal egg counts and generic determination of third stage larvae was performed. Results indicated that six different species of gastrointestinal tract parasites were identified in camels. Single treatment of closantel plus albendazole mixture reduced egg counts in camels by 100 % , 100 % , 98 % and 77 % for Haemonchus longistipes , Ascaris spp . , Monezia expansa and Fasciola hepatica , respectively . However, administration of the drug twice on the base of 2 weeks apart significantly raised the efficacy of the drug for clearance of the parasites from 92.5% to 100% in camels infected with various parasites. Camels were not adversely affected by treatment.

https://pubmed.ncbi.nlm.nih.gov/10321589/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Efficacy of closantel plus albendazole liquid suspension against natural infection of gastrointestinal parasites in camels. Oral administration of closantel in a dose of 10 mg/kg plus albendazole in a dose of 5 mg/kg liquid suspension was studied in 75 camels naturally infected with various types of gastrointestinal parasites. The camels involved were 15 pregnant she-camels, 20 non-pregnant she-camels and 40 male camels of various ages. Each camel received a single oral dose of closantel (10 mg/kg) plus albendazole (5 mg/kg) orally. Two weeks later, 20 camels of this group were re-dosed again with the same dose of the anthelmintic. Fecal samples were collected per rectum from all camels at the time of treatment and again 14 and 42 days post treatment. Fecal egg counts and generic determination of third stage larvae was performed. Results indicated that six different species of gastrointestinal tract parasites were identified in camels. Single treatment of closantel plus albendazole mixture reduced egg counts in camels by 100 % , 100 % , 98 % and 77 % for Haemonchus longistipes , Ascaris spp . , Monezia expansa and Fasciola hepatica , respectively . However, administration of the drug twice on the base of 2 weeks apart significantly raised the efficacy of the drug for clearance of the parasites from 92.5% to 100% in camels infected with various parasites. Camels were not adversely affected by treatment. ### Response: closantel, albendazole

a810b68cf7ccc6138320048a4167e583

In contrast to patients receiving lidocaine , older patients receiving tetracaine experienced significantly less overall pain and discomfort , unpleasant taste , and dyspnea .

A prospective, randomized, double-blind study comparing the efficacy of topical anesthetics in nasal endoscopy. Transnasal endoscopy is commonly performed in an outpatient otolaryngology setting. Patients are typically administered a topical anesthetic and decongestant prior to this procedure to alleviate discomfort and improve visualization. There is no consensus on which topical anesthetic is most effective in optimizing patient experience during the procedure. ### objective To determine whether there is a difference in the efficacy between atomized 2% tetracaine and 4% lidocaine as a topical anesthetic prior to transnasal endoscopy. ### Study Design Prospective, randomized, double-blind study. ### methods A total of 99 patients received oxymetazoline and were randomized to receive either 2% tetracaine or 4% lidocaine prior to transnasal endoscopy. Immediately following the procedure, participants completed a survey assessing level of discomfort and other adverse symptoms pertaining to the procedure using a 10-point visual analog scale (VAS). ### results There were no significant differences in VAS scores between the lidocaine and tetracaine groups. There were also no significant differences between genders in overall VAS scores and in the lidocaine and tetracaine subgroups. Older patients demonstrated significantly less discomfort or a sensation of bad taste overall. In contrast to patients receiving lidocaine , older patients receiving tetracaine experienced significantly less overall pain and discomfort , unpleasant taste , and dyspnea . ### conclusion In patients undergoing transnasal endoscopy, use of either 2% tetracaine or 4% lidocaine has similar effect. tetracaine may be a better choice in older patients, however.

https://pubmed.ncbi.nlm.nih.gov/23404424/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: A prospective, randomized, double-blind study comparing the efficacy of topical anesthetics in nasal endoscopy. Transnasal endoscopy is commonly performed in an outpatient otolaryngology setting. Patients are typically administered a topical anesthetic and decongestant prior to this procedure to alleviate discomfort and improve visualization. There is no consensus on which topical anesthetic is most effective in optimizing patient experience during the procedure. ### objective To determine whether there is a difference in the efficacy between atomized 2% tetracaine and 4% lidocaine as a topical anesthetic prior to transnasal endoscopy. ### Study Design Prospective, randomized, double-blind study. ### methods A total of 99 patients received oxymetazoline and were randomized to receive either 2% tetracaine or 4% lidocaine prior to transnasal endoscopy. Immediately following the procedure, participants completed a survey assessing level of discomfort and other adverse symptoms pertaining to the procedure using a 10-point visual analog scale (VAS). ### results There were no significant differences in VAS scores between the lidocaine and tetracaine groups. There were also no significant differences between genders in overall VAS scores and in the lidocaine and tetracaine subgroups. Older patients demonstrated significantly less discomfort or a sensation of bad taste overall. In contrast to patients receiving lidocaine , older patients receiving tetracaine experienced significantly less overall pain and discomfort , unpleasant taste , and dyspnea . ### conclusion In patients undergoing transnasal endoscopy, use of either 2% tetracaine or 4% lidocaine has similar effect. tetracaine may be a better choice in older patients, however. ### Response: lidocaine, tetracaine

8426f8e8f60a6c637801b577610e05d9

Second-line chemotherapy was also ineffective ; therefore , the bevacizumab and irinotecan were given after a third gross-total resection of the tumor .

Long-term efficacy of bevacizumab and irinotecan in recurrent pediatric glioblastoma. A 5-year-old boy with glioblastoma relapsed soon after postoperative irradiation in combination with temozolomide. Second-line chemotherapy was also ineffective ; therefore , the bevacizumab and irinotecan were given after a third gross-total resection of the tumor . Treatment was interrupted for 1 month due to development of posterior reversible encephalopathy syndrome, but was re-initiated at a lower dose of bevacizumab with prolonged intervals between treatments. The patient was alive and disease free 2 years after initial diagnosis. bevacizumab and irinotecan are a promising regimen for pediatric cases of recurrent glioblastoma after gross-total resection, although the optimal treatment schedule must be determined on a patient-by-patient basis.

https://pubmed.ncbi.nlm.nih.gov/25711258/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Long-term efficacy of bevacizumab and irinotecan in recurrent pediatric glioblastoma. A 5-year-old boy with glioblastoma relapsed soon after postoperative irradiation in combination with temozolomide. Second-line chemotherapy was also ineffective ; therefore , the bevacizumab and irinotecan were given after a third gross-total resection of the tumor . Treatment was interrupted for 1 month due to development of posterior reversible encephalopathy syndrome, but was re-initiated at a lower dose of bevacizumab with prolonged intervals between treatments. The patient was alive and disease free 2 years after initial diagnosis. bevacizumab and irinotecan are a promising regimen for pediatric cases of recurrent glioblastoma after gross-total resection, although the optimal treatment schedule must be determined on a patient-by-patient basis. ### Response: bevacizumab, irinotecan

532c3c76c61f8d9eb020f295bd8cbfc8

In unselected patients with advanced HCC immunotherapeutics , namely the programmed cell death-1 ( PD-1 ) antibodies , nivolumab and pembrolizumab have shown promising efficacy in therapy-naïve , as well as pre-treated patients with advanced HCC .

Recent developments with immunotherapy for hepatocellular carcinoma. Immunotherapy is on the way to become the new standard of care for advanced hepatocellular carcinoma (HCC) worldwide. With higher rates of objective responses, and overall less side effects compared to tyrosine-kinase inhibitors (TKIs) immunotherapeutics will probably replace sorafenib from standard first-line treatment. ### Areas Covered This review covers recent clinical data on systemic agents and ongoing trials in patients with advanced HCC focusing on immunotherapy. ### Expert Opinion In unselected patients with advanced HCC immunotherapeutics , namely the programmed cell death-1 ( PD-1 ) antibodies , nivolumab and pembrolizumab have shown promising efficacy in therapy-naïve , as well as pre-treated patients with advanced HCC . However, only 10-20 percent of treated patients show an objective and durable response to the indicated therapeutics. Therefore, combination therapies including different immunotherapeutics, e.g. PD-1/programmed cell death 1 ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies, or combinations of immunotherapeutics and small molecules, or bifunctional antibodies will be needed to improve response rates. ### abbreviations HCC: hepatocellular carcinoma; TKI: tyrosine-kinase inhibitors; PD-1: programmed death receptor-1; PD-L1: programmed cell death 1 ligand 1; CTLA-4: cytotoxic T-lymphocyte-associated Protein 4; CAR-T: chimeric T cell receptors; TACE: transarterial chemoembolization; SIRT: selective internal radiation therapy; SBRT: stereotactic body radiation therapy; VEGF: vascular endothelial growth factor; MEK: mitogen-activated protein kinase kinase; NK cell: natural killer cell; TGFβ: transforming growth factor-β; OV: Oncolytic viruses; PFU: plaque-forming unit.

https://pubmed.ncbi.nlm.nih.gov/29995439/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Recent developments with immunotherapy for hepatocellular carcinoma. Immunotherapy is on the way to become the new standard of care for advanced hepatocellular carcinoma (HCC) worldwide. With higher rates of objective responses, and overall less side effects compared to tyrosine-kinase inhibitors (TKIs) immunotherapeutics will probably replace sorafenib from standard first-line treatment. ### Areas Covered This review covers recent clinical data on systemic agents and ongoing trials in patients with advanced HCC focusing on immunotherapy. ### Expert Opinion In unselected patients with advanced HCC immunotherapeutics , namely the programmed cell death-1 ( PD-1 ) antibodies , nivolumab and pembrolizumab have shown promising efficacy in therapy-naïve , as well as pre-treated patients with advanced HCC . However, only 10-20 percent of treated patients show an objective and durable response to the indicated therapeutics. Therefore, combination therapies including different immunotherapeutics, e.g. PD-1/programmed cell death 1 ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies, or combinations of immunotherapeutics and small molecules, or bifunctional antibodies will be needed to improve response rates. ### abbreviations HCC: hepatocellular carcinoma; TKI: tyrosine-kinase inhibitors; PD-1: programmed death receptor-1; PD-L1: programmed cell death 1 ligand 1; CTLA-4: cytotoxic T-lymphocyte-associated Protein 4; CAR-T: chimeric T cell receptors; TACE: transarterial chemoembolization; SIRT: selective internal radiation therapy; SBRT: stereotactic body radiation therapy; VEGF: vascular endothelial growth factor; MEK: mitogen-activated protein kinase kinase; NK cell: natural killer cell; TGFβ: transforming growth factor-β; OV: Oncolytic viruses; PFU: plaque-forming unit. ### Response: nivolumab, pembrolizumab

fa1e8b298a512fc856c1e81df55911b0

Treatment with rapamycin and paclitaxel resulted in decreased phosphorylation of S6 and 4E-BP1 , two critical downstream targets of the mTOR pathway .

Rapamycin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and induction of apoptosis. Mammalian target of rapamycin (mTOR) inhibitors modulate signaling pathways involved in cell cycle progression, and recent phase II trials demonstrate activity in patients with endometrial cancer. Our objective was to examine the effects of combination therapy with rapamycin and paclitaxel in endometrial cancer cell lines. paclitaxel inhibited proliferation in a dose-dependent manner in both cell lines with IC(50) values of 0.1-0.5 nM and 1-5 nM for Ishikawa and ECC-1 cells, respectively. To assess synergy of paclitaxel and rapamycin, the combination index (CI) was calculated by the method of Chou and Talalay. Simultaneous exposure of cells to various doses of paclitaxel in combination with rapamycin (1 nM) resulted in a significant synergistic anti-proliferative effect (CI <1, range 0.131-0.920). rapamycin alone did not induce apoptosis, but combined treatment with paclitaxel increased apoptosis over that of paclitaxel alone. Treatment with rapamycin and paclitaxel resulted in decreased phosphorylation of S6 and 4E-BP1 , two critical downstream targets of the mTOR pathway . rapamycin decreased hTERT mRNA expression by real-time RT-PCR while paclitaxel alone had no effect on telomerase activity. paclitaxel increased polymerization and acetylation of tubulin, and rapamycin appeared to enhance this effect. Thus, in conclusion, we demonstrate that rapamycin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation, induction of apoptosis and potentially increased polymerization and acetylation of tubulin. This suggests that the combination of rapamycin and paclitaxel may be a promising effective targeted therapy for endometrial cancer.

https://pubmed.ncbi.nlm.nih.gov/19688827/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Rapamycin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and induction of apoptosis. Mammalian target of rapamycin (mTOR) inhibitors modulate signaling pathways involved in cell cycle progression, and recent phase II trials demonstrate activity in patients with endometrial cancer. Our objective was to examine the effects of combination therapy with rapamycin and paclitaxel in endometrial cancer cell lines. paclitaxel inhibited proliferation in a dose-dependent manner in both cell lines with IC(50) values of 0.1-0.5 nM and 1-5 nM for Ishikawa and ECC-1 cells, respectively. To assess synergy of paclitaxel and rapamycin, the combination index (CI) was calculated by the method of Chou and Talalay. Simultaneous exposure of cells to various doses of paclitaxel in combination with rapamycin (1 nM) resulted in a significant synergistic anti-proliferative effect (CI <1, range 0.131-0.920). rapamycin alone did not induce apoptosis, but combined treatment with paclitaxel increased apoptosis over that of paclitaxel alone. Treatment with rapamycin and paclitaxel resulted in decreased phosphorylation of S6 and 4E-BP1 , two critical downstream targets of the mTOR pathway . rapamycin decreased hTERT mRNA expression by real-time RT-PCR while paclitaxel alone had no effect on telomerase activity. paclitaxel increased polymerization and acetylation of tubulin, and rapamycin appeared to enhance this effect. Thus, in conclusion, we demonstrate that rapamycin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation, induction of apoptosis and potentially increased polymerization and acetylation of tubulin. This suggests that the combination of rapamycin and paclitaxel may be a promising effective targeted therapy for endometrial cancer. ### Response: rapamycin, paclitaxel

d49e128f648e789ddc390d1f87e75031

Conversely , the IMbrave150 trial recently showed that , among patients with previously untreated unresectable HCC , treatment with atezolizumab plus bevacizumab resulted in significantly longer overall survival and progression-free survival compared to sorafenib monotherapy .

Biochemical predictors of response to immune checkpoint inhibitors in unresectable hepatocellular carcinoma. Hepatocellular carcinoma (HCC) represents the most commonly diagnosed liver cancer worldwide, and the overall survival of patients with unresectable disease is poor. In the last five years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment scenario of several hematological and solid tumors, and these agents have been actively explored in unresectable HCC. Firstly, promising findings of phase I and II clinical studies reporting durable responses and a tolerable safety profile have led to the assessment of ICIs as single agents in phase III clinical studies; however, the latter have provided controversial results, and the activity of ICI monotherapy seems limited to a small subgroup of patients. Conversely , the IMbrave150 trial recently showed that , among patients with previously untreated unresectable HCC , treatment with atezolizumab plus bevacizumab resulted in significantly longer overall survival and progression-free survival compared to sorafenib monotherapy . In addition, the activity of several other ICIs is under investigation, as combination immunotherapy as well as combinations of immunotherapy with antiangiogenic agents. Nonetheless, there are currently no validated predictive biomarkers able to guide treatment choice in this setting, where the identification of specific predictors of response to ICIs represents a major challenge. In this review, we aim to provide a critical overview of recent evidence on biochemical predictors of response to ICIs in patients with unresectable HCC, especially focusing on PD-L1, TMB, MSI, and other emerging biomarkers.

https://pubmed.ncbi.nlm.nih.gov/33549983/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Biochemical predictors of response to immune checkpoint inhibitors in unresectable hepatocellular carcinoma. Hepatocellular carcinoma (HCC) represents the most commonly diagnosed liver cancer worldwide, and the overall survival of patients with unresectable disease is poor. In the last five years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment scenario of several hematological and solid tumors, and these agents have been actively explored in unresectable HCC. Firstly, promising findings of phase I and II clinical studies reporting durable responses and a tolerable safety profile have led to the assessment of ICIs as single agents in phase III clinical studies; however, the latter have provided controversial results, and the activity of ICI monotherapy seems limited to a small subgroup of patients. Conversely , the IMbrave150 trial recently showed that , among patients with previously untreated unresectable HCC , treatment with atezolizumab plus bevacizumab resulted in significantly longer overall survival and progression-free survival compared to sorafenib monotherapy . In addition, the activity of several other ICIs is under investigation, as combination immunotherapy as well as combinations of immunotherapy with antiangiogenic agents. Nonetheless, there are currently no validated predictive biomarkers able to guide treatment choice in this setting, where the identification of specific predictors of response to ICIs represents a major challenge. In this review, we aim to provide a critical overview of recent evidence on biochemical predictors of response to ICIs in patients with unresectable HCC, especially focusing on PD-L1, TMB, MSI, and other emerging biomarkers. ### Response: atezolizumab, bevacizumab, sorafenib

400a1eae25bec51f7399dce5efbc4014

Evaluation of tamoxifen plus letrozole with assessment of pharmacokinetic interaction in postmenopausal women with metastatic breast cancer .

Evaluation of tamoxifen plus letrozole with assessment of pharmacokinetic interaction in postmenopausal women with metastatic breast cancer . The goals of this clinical trial involving postmenopausal women with metastatic breast cancer were to: (a) examine the effects of letrozole on tamoxifen (TAM) pharmacokinetics; (b) examine estrogen suppression in patients receiving TAM plus letrozole; and (c) evaluate tolerability, toxicity, objective response, and time to progression for the combination. Postmenopausal women with measurable or evaluable metastatic breast cancer received TAM (20 mg daily) for 6 weeks, and then letrozole (2.5 mg daily) was added. To examine for any effect of letrozole on the levels of TAM and two metabolites [N-desmethyl-TAM and 4-hydroxy-TAM], serum samples were obtained at 6, 12, 18, and 24 weeks. To examine for aromatase inhibition, serum samples were obtained before treatment and at 6, 12, 18, and 24 weeks for estradiol, estrone (E1) E1 sulfate, and sex hormone-binding globulin. A total of 34 patients were entered on this trial, and 23 patients were still on study at week 24, 18 of whom had blood samples available at both week 6 and week 24. The 95% confidence interval for the mean difference between levels at week 24 and levels at week 6 was -34 to 15 ng/ml for TAM, -35 to 45 ng/ml for N-desmethyl-TAM, and -1 to 2 for 4-hydroxy-TAM. For estradiol, a significant decrease (median, 88.5%; range, 73.7-95.2%) was identified after 6 weeks of letrozole, which was maintained for an additional 12 weeks. Similar significant reductions were identified for E1. E1 sulfate levels increased after 6 weeks of TAM alone but then decreased significantly after the addition of letrozole. Sex hormone-binding globulin levels were significantly elevated after 6 weeks of TAM alone and remained elevated after the addition of letrozole. Six of the 34 patients (17.6%) achieved an objective response (95% confidence interval, 6.8-34.5%), with a median time to disease progression of 7.6 months. There was no indication of a systematic decrease in TAM, N-desmethyl-TAM, or 4-hydroxy-TAM after the additional of letrozole. Estrogen suppression induced by letrozole was substantial despite the concomitant administration of TAM. The antitumor effect of TAM plus letrozole was less than expected.

https://pubmed.ncbi.nlm.nih.gov/10430063/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Evaluation of tamoxifen plus letrozole with assessment of pharmacokinetic interaction in postmenopausal women with metastatic breast cancer . The goals of this clinical trial involving postmenopausal women with metastatic breast cancer were to: (a) examine the effects of letrozole on tamoxifen (TAM) pharmacokinetics; (b) examine estrogen suppression in patients receiving TAM plus letrozole; and (c) evaluate tolerability, toxicity, objective response, and time to progression for the combination. Postmenopausal women with measurable or evaluable metastatic breast cancer received TAM (20 mg daily) for 6 weeks, and then letrozole (2.5 mg daily) was added. To examine for any effect of letrozole on the levels of TAM and two metabolites [N-desmethyl-TAM and 4-hydroxy-TAM], serum samples were obtained at 6, 12, 18, and 24 weeks. To examine for aromatase inhibition, serum samples were obtained before treatment and at 6, 12, 18, and 24 weeks for estradiol, estrone (E1) E1 sulfate, and sex hormone-binding globulin. A total of 34 patients were entered on this trial, and 23 patients were still on study at week 24, 18 of whom had blood samples available at both week 6 and week 24. The 95% confidence interval for the mean difference between levels at week 24 and levels at week 6 was -34 to 15 ng/ml for TAM, -35 to 45 ng/ml for N-desmethyl-TAM, and -1 to 2 for 4-hydroxy-TAM. For estradiol, a significant decrease (median, 88.5%; range, 73.7-95.2%) was identified after 6 weeks of letrozole, which was maintained for an additional 12 weeks. Similar significant reductions were identified for E1. E1 sulfate levels increased after 6 weeks of TAM alone but then decreased significantly after the addition of letrozole. Sex hormone-binding globulin levels were significantly elevated after 6 weeks of TAM alone and remained elevated after the addition of letrozole. Six of the 34 patients (17.6%) achieved an objective response (95% confidence interval, 6.8-34.5%), with a median time to disease progression of 7.6 months. There was no indication of a systematic decrease in TAM, N-desmethyl-TAM, or 4-hydroxy-TAM after the additional of letrozole. Estrogen suppression induced by letrozole was substantial despite the concomitant administration of TAM. The antitumor effect of TAM plus letrozole was less than expected. ### Response: tamoxifen, letrozole

0a4bbd89b0116fe38b5aa37d3710db43

Moreover , the BCR/ABL1 inhibitors nilotinib and ponatinib were found to decrease STAT5 activity and CD25 expression in KU812 cells and primary CML LSCs .

Identification of CD25 as STAT5-Dependent Growth Regulator of Leukemic Stem Cells in Ph+ CML. In chronic myelogenous leukemia (CML), leukemic stem cells (LSC) represent a critical target of therapy. However, little is known about markers and targets expressed by LSCs. The aim of this project was to identify novel relevant markers of CML LSCs. ### Experimental Design CML LSCs were examined by flow cytometry, qPCR, and various bioassays. In addition, we examined the multipotent CD25(+)CML cell line KU812. ### results In contrast to normal hematopoietic stem cells, CD34(+)/CD38(-)CML LSCs expressed the IL-2 receptor alpha chain, IL-2RA (CD25). STAT5 was found to induce expression of CD25 in Lin(-)/Sca-1(+)/Kit(+)stem cells in C57Bl/6 mice. Correspondingly, shRNA-induced STAT5 depletion resulted in decreased CD25 expression in KU812 cells. Moreover , the BCR/ABL1 inhibitors nilotinib and ponatinib were found to decrease STAT5 activity and CD25 expression in KU812 cells and primary CML LSCs . A CD25-targeting shRNA was found to augment proliferation of KU812 cellsin vitroand their engraftmentin vivoin NOD/SCID-IL-2Rγ(-/-)mice. In drug-screening experiments, the PI3K/mTOR blocker BEZ235 promoted the expression of STAT5 and CD25 in CML cells. Finally, we found that BEZ235 produces synergistic antineoplastic effects on CML cells when applied in combination with nilotinib or ponatinib. ### conclusions CD25 is a novel STAT5-dependent marker of CML LSCs and may be useful for LSC detection and LSC isolation in clinical practice and basic science. Moreover, CD25 serves as a growth regulator of CML LSCs, which may have biologic and clinical implications and may pave the way for the development of new more effective LSC-eradicating treatment strategies in CML.

https://pubmed.ncbi.nlm.nih.gov/26607600/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Identification of CD25 as STAT5-Dependent Growth Regulator of Leukemic Stem Cells in Ph+ CML. In chronic myelogenous leukemia (CML), leukemic stem cells (LSC) represent a critical target of therapy. However, little is known about markers and targets expressed by LSCs. The aim of this project was to identify novel relevant markers of CML LSCs. ### Experimental Design CML LSCs were examined by flow cytometry, qPCR, and various bioassays. In addition, we examined the multipotent CD25(+)CML cell line KU812. ### results In contrast to normal hematopoietic stem cells, CD34(+)/CD38(-)CML LSCs expressed the IL-2 receptor alpha chain, IL-2RA (CD25). STAT5 was found to induce expression of CD25 in Lin(-)/Sca-1(+)/Kit(+)stem cells in C57Bl/6 mice. Correspondingly, shRNA-induced STAT5 depletion resulted in decreased CD25 expression in KU812 cells. Moreover , the BCR/ABL1 inhibitors nilotinib and ponatinib were found to decrease STAT5 activity and CD25 expression in KU812 cells and primary CML LSCs . A CD25-targeting shRNA was found to augment proliferation of KU812 cellsin vitroand their engraftmentin vivoin NOD/SCID-IL-2Rγ(-/-)mice. In drug-screening experiments, the PI3K/mTOR blocker BEZ235 promoted the expression of STAT5 and CD25 in CML cells. Finally, we found that BEZ235 produces synergistic antineoplastic effects on CML cells when applied in combination with nilotinib or ponatinib. ### conclusions CD25 is a novel STAT5-dependent marker of CML LSCs and may be useful for LSC detection and LSC isolation in clinical practice and basic science. Moreover, CD25 serves as a growth regulator of CML LSCs, which may have biologic and clinical implications and may pave the way for the development of new more effective LSC-eradicating treatment strategies in CML. ### Response: nilotinib, ponatinib

4f3b59fab506326763dc670b527a345f

The EVERLAR study reports prospective data of somatostatin analogue in combination with everolimus in nonfunctioning gastrointestinal neuroendocrine tumors suggesting meaningful activity and favorable toxicity profile that supports drug combination in this setting .

Phase II Study of Everolimus and Octreotide LAR in Patients with Nonfunctioning Gastrointestinal Neuroendocrine Tumors: The GETNE1003_EVERLAR Study. Antitumor activity of the combination of somatostatin analogues (SSAs) and the mammalian target of rapamycin (mTOR) inhibitor everolimus in patients with neuroendocrine tumors (NETs) has been reported but not confirmed in prospective trials. ### Materials And Methods This prospective, multicenter, single-arm phase II EVERLAR study evaluated everolimus 10 mg/day and the SSA octreotide 30 mg every 28 days in patients with advanced nonfunctioning well-differentiated gastrointestinal NETs (GI-NETs) that progressed in the last 12 months (ClinicalTrials.gov NCT01567488). Prior treatment with SSAs and any systemic or locoregional therapy was allowed except for mTOR inhibitors. Patients continued treatment until disease progression or unacceptable adverse events (AEs). The primary endpoint was progression-free survival (PFS) at 12 months; secondary endpoints included early biochemical response, objective response rate (ORR) by RECIST v1.0, overall survival (OS), AEs, activation of mTOR pathway (insulin-like growth factor 1 receptor [IGF1R] and phosphoS6 [pS6] expression). ### results Forty-three patients were included in the intent-to-treat analyses. After 12 months of treatment, 62.3% (95% confidence interval [CI] 48%-77%) of patients had not progressed or died. The 24-month PFS rate was 43.6% (95% CI 29%-58%). The confirmed ORR was 2.3%, and stable disease was 58.1%. Median OS was not reached after 24 months of median follow-up. Dose reductions and temporary interruptions due to AEs were required in 14 (33%) and 33 (77%) patients, respectively. The most frequent AEs were diarrhea, asthenia, mucositis, rash, and hyperglycemia. No correlation was observed between IGFR1 and pS6 expression and PFS/OS. ### conclusion The everolimus-octreotide combination provided clinically relevant efficacy in nonfunctioning GI-NETs, similar to the results of RADIANT-2 in functioning setting. ### Implications For Practice The EVERLAR study reports prospective data of somatostatin analogue in combination with everolimus in nonfunctioning gastrointestinal neuroendocrine tumors suggesting meaningful activity and favorable toxicity profile that supports drug combination in this setting .

https://pubmed.ncbi.nlm.nih.gov/29794066/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Phase II Study of Everolimus and Octreotide LAR in Patients with Nonfunctioning Gastrointestinal Neuroendocrine Tumors: The GETNE1003_EVERLAR Study. Antitumor activity of the combination of somatostatin analogues (SSAs) and the mammalian target of rapamycin (mTOR) inhibitor everolimus in patients with neuroendocrine tumors (NETs) has been reported but not confirmed in prospective trials. ### Materials And Methods This prospective, multicenter, single-arm phase II EVERLAR study evaluated everolimus 10 mg/day and the SSA octreotide 30 mg every 28 days in patients with advanced nonfunctioning well-differentiated gastrointestinal NETs (GI-NETs) that progressed in the last 12 months (ClinicalTrials.gov NCT01567488). Prior treatment with SSAs and any systemic or locoregional therapy was allowed except for mTOR inhibitors. Patients continued treatment until disease progression or unacceptable adverse events (AEs). The primary endpoint was progression-free survival (PFS) at 12 months; secondary endpoints included early biochemical response, objective response rate (ORR) by RECIST v1.0, overall survival (OS), AEs, activation of mTOR pathway (insulin-like growth factor 1 receptor [IGF1R] and phosphoS6 [pS6] expression). ### results Forty-three patients were included in the intent-to-treat analyses. After 12 months of treatment, 62.3% (95% confidence interval [CI] 48%-77%) of patients had not progressed or died. The 24-month PFS rate was 43.6% (95% CI 29%-58%). The confirmed ORR was 2.3%, and stable disease was 58.1%. Median OS was not reached after 24 months of median follow-up. Dose reductions and temporary interruptions due to AEs were required in 14 (33%) and 33 (77%) patients, respectively. The most frequent AEs were diarrhea, asthenia, mucositis, rash, and hyperglycemia. No correlation was observed between IGFR1 and pS6 expression and PFS/OS. ### conclusion The everolimus-octreotide combination provided clinically relevant efficacy in nonfunctioning GI-NETs, similar to the results of RADIANT-2 in functioning setting. ### Implications For Practice The EVERLAR study reports prospective data of somatostatin analogue in combination with everolimus in nonfunctioning gastrointestinal neuroendocrine tumors suggesting meaningful activity and favorable toxicity profile that supports drug combination in this setting . ### Response: somatostatin, everolimus

90bfe4266085a7725c0b30a40fca9cc6

Synergism between anti-HER2 monoclonal antibody ( trastuzumab ) and paclitaxel has been shown in vitro and in vivo .

Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer. Synergism between anti-HER2 monoclonal antibody ( trastuzumab ) and paclitaxel has been shown in vitro and in vivo . In previous experiences, weekly administration of trastuzumab and paclitaxel has shown significant activity in metastatic breast cancer. In this phase II study, we evaluated the activity and the toxicity of this weekly regimen in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer. Between November 1999 and July 2001, 25 patients were treated with trastuzumab (4 mg kg(-1) i.v. loading dose followed by 2 mg kg(-1) i.v. week(-1)) and paclitaxel (60-90 mg m(-2) h(-1) i.v. infusion week(-1)). The treatment was planned to continue until disease progression or prohibitive toxicity; in patients with responsive or stable disease, after 6 months of therapy, the decision to stop paclitaxel while continuing weekly trastuzumab was left to the physicians' judgement. At the median follow-up of 19.6 months (range 9.2-38.1), all patients are evaluable for response and toxicity. We obtained four (16%) complete responses (CR), 10 (40%) partial responses (PR), four (16%) stable diseases and seven (28%) disease progressions. The response rate (CR+PR) was 56% (95% CI, 36.5-75.5%). The median duration of response was 10.4 months (range 4.1-24.2+). Median time to progression was 8.6 months (range 2.5-24.2+). The toxicity was mild; five patients experienced fever and chills during the first infusion of trastuzumab (20%); leukopenia grade 2 was recorded in one patient (4%). Two patients (8%) came off study for grade 3 cardiotoxicity (after 9 and 17 weeks of treatment, respectively): both had already received anthracyclines and taxanes. Onycholysis grade 2 was observed in five patients (20%). These results confirm that weekly administration of trastuzumab and paclitaxel is active in anthracycline- and taxane-pretreated metastatic breast cancer patients HER2-overexpressing. Since cardiac disfunctions grade 3 were observed (8%), we recommend that cardiac function should be monitored in these patients.

https://pubmed.ncbi.nlm.nih.gov/14710203/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer. Synergism between anti-HER2 monoclonal antibody ( trastuzumab ) and paclitaxel has been shown in vitro and in vivo . In previous experiences, weekly administration of trastuzumab and paclitaxel has shown significant activity in metastatic breast cancer. In this phase II study, we evaluated the activity and the toxicity of this weekly regimen in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer. Between November 1999 and July 2001, 25 patients were treated with trastuzumab (4 mg kg(-1) i.v. loading dose followed by 2 mg kg(-1) i.v. week(-1)) and paclitaxel (60-90 mg m(-2) h(-1) i.v. infusion week(-1)). The treatment was planned to continue until disease progression or prohibitive toxicity; in patients with responsive or stable disease, after 6 months of therapy, the decision to stop paclitaxel while continuing weekly trastuzumab was left to the physicians' judgement. At the median follow-up of 19.6 months (range 9.2-38.1), all patients are evaluable for response and toxicity. We obtained four (16%) complete responses (CR), 10 (40%) partial responses (PR), four (16%) stable diseases and seven (28%) disease progressions. The response rate (CR+PR) was 56% (95% CI, 36.5-75.5%). The median duration of response was 10.4 months (range 4.1-24.2+). Median time to progression was 8.6 months (range 2.5-24.2+). The toxicity was mild; five patients experienced fever and chills during the first infusion of trastuzumab (20%); leukopenia grade 2 was recorded in one patient (4%). Two patients (8%) came off study for grade 3 cardiotoxicity (after 9 and 17 weeks of treatment, respectively): both had already received anthracyclines and taxanes. Onycholysis grade 2 was observed in five patients (20%). These results confirm that weekly administration of trastuzumab and paclitaxel is active in anthracycline- and taxane-pretreated metastatic breast cancer patients HER2-overexpressing. Since cardiac disfunctions grade 3 were observed (8%), we recommend that cardiac function should be monitored in these patients. ### Response: trastuzumab, paclitaxel

71f038d703d77df97e666dc522f17849

Between September 1998 and December 1999 , we treated 25 patients at risk for post-operative renal dysfunction ( high-risk basiliximab group ) with the new induction regimen and another 33 patients not at risk ( low-risk CsA group ) for renal dysfunction with our standard cyclosporine protocol .

Induction therapy with basiliximab allows delayed initiation of cyclosporine and preserves renal function after cardiac transplantation. cyclosporine (CsA) is frequently initiated as induction therapy in patients undergoing orthotopic heart transplantation, but our experience has identified a significant rate of post-operative renal dysfunction. We therefore devised a renal-sparing cyclosporine-free induction regimen consisting of the early administration basiliximab, an interleukin-2 receptor monoclonal antibody, followed by the late initiation of cyclosporine on post-operative Day 4. ### methods Between September 1998 and December 1999 , we treated 25 patients at risk for post-operative renal dysfunction ( high-risk basiliximab group ) with the new induction regimen and another 33 patients not at risk ( low-risk CsA group ) for renal dysfunction with our standard cyclosporine protocol . We identified a historical control group (1996 through 1998) of 32 patients at risk for renal dysfunction (high-risk CsA group) who had received our standard cyclosporine protocol. ### results The increase in serum creatinine levels after transplantation was less in the high-risk basiliximab group (-0.1 +/- 0.7) than in the high-risk CsA group (0.5 +/- 1.0, p < 0.02) and comparable to the low-risk CsA group (0.03 +/- 0.6). The basiliximab protocol did not increase rejection; the percentage of rejection episodes was high-risk basiliximab, 0; high-risk CsA, 13; and low-risk CsA, 3 (p = .13). ### conclusion basiliximab induction therapy allows delayed initiation of cyclosporine after cardiac transplantation without an increase in rejection and reduces the risk of post-operative renal dysfunction.

https://pubmed.ncbi.nlm.nih.gov/16143252/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Induction therapy with basiliximab allows delayed initiation of cyclosporine and preserves renal function after cardiac transplantation. cyclosporine (CsA) is frequently initiated as induction therapy in patients undergoing orthotopic heart transplantation, but our experience has identified a significant rate of post-operative renal dysfunction. We therefore devised a renal-sparing cyclosporine-free induction regimen consisting of the early administration basiliximab, an interleukin-2 receptor monoclonal antibody, followed by the late initiation of cyclosporine on post-operative Day 4. ### methods Between September 1998 and December 1999 , we treated 25 patients at risk for post-operative renal dysfunction ( high-risk basiliximab group ) with the new induction regimen and another 33 patients not at risk ( low-risk CsA group ) for renal dysfunction with our standard cyclosporine protocol . We identified a historical control group (1996 through 1998) of 32 patients at risk for renal dysfunction (high-risk CsA group) who had received our standard cyclosporine protocol. ### results The increase in serum creatinine levels after transplantation was less in the high-risk basiliximab group (-0.1 +/- 0.7) than in the high-risk CsA group (0.5 +/- 1.0, p < 0.02) and comparable to the low-risk CsA group (0.03 +/- 0.6). The basiliximab protocol did not increase rejection; the percentage of rejection episodes was high-risk basiliximab, 0; high-risk CsA, 13; and low-risk CsA, 3 (p = .13). ### conclusion basiliximab induction therapy allows delayed initiation of cyclosporine after cardiac transplantation without an increase in rejection and reduces the risk of post-operative renal dysfunction. ### Response: basiliximab, cyclosporine

afb487e5f3a9ba9b35526d05826560e6

Cardiac events occurred after posaconazole administration , incriminating posaconazole use , alone or in combination with voriconazole , as the culpable agent .

Long QT Syndrome Leading to Multiple Cardiac Arrests After Posaconazole Administration in an Immune-Compromised Patient with Sepsis: An Unusual Case Report. We present the case of a septic patient with severe immunodeficiency, who developed QT interval prolongation followed by episodes of lethal cardiac arrhythmia. Cardiac events occurred after posaconazole administration , incriminating posaconazole use , alone or in combination with voriconazole , as the culpable agent . ### Case Report A 26-year-old female patient underwent orthopedic surgery to remove ectopic calcifications in her left hip joint. On the first post-operative day she became septic due to a surgical wound infection. Despite being treated according to the therapeutic protocols for sepsis, no clinical improvement was noticed and further assessment revealed an underlying immunodeficiency. Considering the underlying immunodeficiency and to that point poor clinical response, an antifungal agent was added to the antibiotic regiment. Following discontinuation of multiple antifungal agents due to adverse effects, posaconazole was administered. posaconazole oral intake was followed by episodes of bradycardia and QT interval prolongation. The patient suffered continuous incidents of cardiac arrest due to polymorphic ventricular tachycardia (torsades des pointes) that degenerated to lethal ventricular fibrillation. posaconazole was immediately discontinued and a temporary pacemaker was installed. The patient finally recovered without any neurological deficit, and was discharged in a good clinical status. ### conclusions Close cardiac monitoring is recommended in cases where posaconazole administration is combined with coexisting risk factors, as they may lead to severe ECG abnormalities and cardiac arrhythmias such as long QT interval syndrome and torsades de pointes. posaconazole interactions with medications metabolized via the CYP3A4 pathway should be considered an additional risk factor for lethal cardiac incidents.

https://pubmed.ncbi.nlm.nih.gov/27125217/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Long QT Syndrome Leading to Multiple Cardiac Arrests After Posaconazole Administration in an Immune-Compromised Patient with Sepsis: An Unusual Case Report. We present the case of a septic patient with severe immunodeficiency, who developed QT interval prolongation followed by episodes of lethal cardiac arrhythmia. Cardiac events occurred after posaconazole administration , incriminating posaconazole use , alone or in combination with voriconazole , as the culpable agent . ### Case Report A 26-year-old female patient underwent orthopedic surgery to remove ectopic calcifications in her left hip joint. On the first post-operative day she became septic due to a surgical wound infection. Despite being treated according to the therapeutic protocols for sepsis, no clinical improvement was noticed and further assessment revealed an underlying immunodeficiency. Considering the underlying immunodeficiency and to that point poor clinical response, an antifungal agent was added to the antibiotic regiment. Following discontinuation of multiple antifungal agents due to adverse effects, posaconazole was administered. posaconazole oral intake was followed by episodes of bradycardia and QT interval prolongation. The patient suffered continuous incidents of cardiac arrest due to polymorphic ventricular tachycardia (torsades des pointes) that degenerated to lethal ventricular fibrillation. posaconazole was immediately discontinued and a temporary pacemaker was installed. The patient finally recovered without any neurological deficit, and was discharged in a good clinical status. ### conclusions Close cardiac monitoring is recommended in cases where posaconazole administration is combined with coexisting risk factors, as they may lead to severe ECG abnormalities and cardiac arrhythmias such as long QT interval syndrome and torsades de pointes. posaconazole interactions with medications metabolized via the CYP3A4 pathway should be considered an additional risk factor for lethal cardiac incidents. ### Response: posaconazole, posaconazole, voriconazole

d27c12a579e30cabf1743a89badedece

Prognostic value of expression of Kit67 , p53 , TopoIIa and GSTP1 for curatively resected advanced gastric cancer patients receiving adjuvant paclitaxel plus capecitabine chemotherapy .

Prognostic value of expression of Kit67 , p53 , TopoIIa and GSTP1 for curatively resected advanced gastric cancer patients receiving adjuvant paclitaxel plus capecitabine chemotherapy . To investigate the role of Kit67, p53, topoisomerase II (TopoII) and glutathione S-transferase P1 (GSTP1) in predicting clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel chemotherapy. ### methodology The clinical data and tissue samples from 136 curatively resected advanced gastric cancer patients receiving capecitabine plus paclitaxel in the third affiliated hospital of Kunming medical university from January 2005 to December 2007 were retrospectively collected and analyzed for Kit67, p53, TopoIIa and GSTP1 expressions by immunohistochemistry. The relationships between expressions of the biomarkers and survival were analyzed. ### results p53 expression were associated with the significantly shorter disease-free survival (DFS) (p<0.001) and overall survival (OS) (p=0.012) in the curatively resected advanced gastric cancer patients receiving capecitabine plus paclitaxel. Kit67, TopoIIa and GSTP1 expressions were not related to DFS and OS. ### conclusions p53 expression positive might predict prognosis in gastric cancer patients who underwent curative surgery followed by adjuvant capecitabine plus paclitaxel chemotherapy. A favorable effect of capecitabine plus paclitaxel might therefore be expected in patients that do not express p53.

https://pubmed.ncbi.nlm.nih.gov/22534478/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Prognostic value of expression of Kit67 , p53 , TopoIIa and GSTP1 for curatively resected advanced gastric cancer patients receiving adjuvant paclitaxel plus capecitabine chemotherapy . To investigate the role of Kit67, p53, topoisomerase II (TopoII) and glutathione S-transferase P1 (GSTP1) in predicting clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel chemotherapy. ### methodology The clinical data and tissue samples from 136 curatively resected advanced gastric cancer patients receiving capecitabine plus paclitaxel in the third affiliated hospital of Kunming medical university from January 2005 to December 2007 were retrospectively collected and analyzed for Kit67, p53, TopoIIa and GSTP1 expressions by immunohistochemistry. The relationships between expressions of the biomarkers and survival were analyzed. ### results p53 expression were associated with the significantly shorter disease-free survival (DFS) (p<0.001) and overall survival (OS) (p=0.012) in the curatively resected advanced gastric cancer patients receiving capecitabine plus paclitaxel. Kit67, TopoIIa and GSTP1 expressions were not related to DFS and OS. ### conclusions p53 expression positive might predict prognosis in gastric cancer patients who underwent curative surgery followed by adjuvant capecitabine plus paclitaxel chemotherapy. A favorable effect of capecitabine plus paclitaxel might therefore be expected in patients that do not express p53. ### Response: paclitaxel, capecitabine

8d395c0462d3164578455a4339b29ea1

The standard adjuvant treatment of colon cancer is fluorouracil plus leucovorin ( FL ) .

Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. The standard adjuvant treatment of colon cancer is fluorouracil plus leucovorin ( FL ) . oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer. We evaluated the efficacy of treatment with FL plus oxaliplatin in the postoperative adjuvant setting. ### methods We randomly assigned 2246 patients who had undergone curative resection for stage II or III colon cancer to receive FL alone or with oxaliplatin for six months. The primary end point was disease-free survival. ### results A total of 1123 patients were randomly assigned to each group. After a median follow-up of 37.9 months, 237 patients in the group given FL plus oxaliplatin had had a cancer-related event, as compared with 293 patients in the FL group (21.1 percent vs. 26.1 percent; hazard ratio for recurrence, 0.77; P=0.002). The rate of disease-free survival at three years was 78.2 percent (95 percent confidence interval, 75.6 to 80.7) in the group given FL plus oxaliplatin and 72.9 percent (95 percent confidence interval, 70.2 to 75.7) in the FL group (P=0.002 by the stratified log-rank test). In the group given FL plus oxaliplatin, the incidence of febrile neutropenia was 1.8 percent, the incidence of gastrointestinal adverse effects was low, and the incidence of grade 3 sensory neuropathy was 12.4 percent during treatment, decreasing to 1.1 percent at one year of follow-up. Six patients in each group died during treatment (death rate, 0.5 percent). ### conclusions Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer.

https://pubmed.ncbi.nlm.nih.gov/15175436/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. The standard adjuvant treatment of colon cancer is fluorouracil plus leucovorin ( FL ) . oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer. We evaluated the efficacy of treatment with FL plus oxaliplatin in the postoperative adjuvant setting. ### methods We randomly assigned 2246 patients who had undergone curative resection for stage II or III colon cancer to receive FL alone or with oxaliplatin for six months. The primary end point was disease-free survival. ### results A total of 1123 patients were randomly assigned to each group. After a median follow-up of 37.9 months, 237 patients in the group given FL plus oxaliplatin had had a cancer-related event, as compared with 293 patients in the FL group (21.1 percent vs. 26.1 percent; hazard ratio for recurrence, 0.77; P=0.002). The rate of disease-free survival at three years was 78.2 percent (95 percent confidence interval, 75.6 to 80.7) in the group given FL plus oxaliplatin and 72.9 percent (95 percent confidence interval, 70.2 to 75.7) in the FL group (P=0.002 by the stratified log-rank test). In the group given FL plus oxaliplatin, the incidence of febrile neutropenia was 1.8 percent, the incidence of gastrointestinal adverse effects was low, and the incidence of grade 3 sensory neuropathy was 12.4 percent during treatment, decreasing to 1.1 percent at one year of follow-up. Six patients in each group died during treatment (death rate, 0.5 percent). ### conclusions Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer. ### Response: fluorouracil, leucovorin

dbe218b8b09950b9c28f7a92e7b5f29d

Effects of ultrasound were similar at baseline and after propranolol but increased after phenylephrine .

Alteration of left ventricular endocardial function by intracavitary high-power ultrasound interacts with volume, inotropic state, and alpha 1-adrenergic stimulation. High-power intracavitary ultrasound abbreviates left ventricular (LV) ejection duration, thereby decreasing mechanical LV performance, presumably by selective impairment of endocardial endothelial function. ### Methods And Results Effects of ultrasound were evaluated in the ejecting LV of anesthetized, open-chest dogs under different conditions of LV volume and contractile state and after mild selective alpha 1-adrenergic stimulation. LV pressures, left atrial pressures, and regional segment lengths were measured in anterior and posterior midwall. A cylindrical ultrasound probe (0.9 MHz, 25 W) mounted on a catheter was inserted into the LV cavity through the apex and was activated for 4 minutes in each condition. In protocol A (n = 7), LV volume was altered with caval vein occlusion and intravenous dextran infusion. The ultrasound probe was activated at low (4.1 +/- 0.9 mm Hg), mid (10.6 +/- 1.5 mm Hg), and high (17.9 +/- 1.8 mm Hg) LV end-diastolic pressure (EDP). Effects of ultrasound were less pronounced at higher EDP. For example, the time interval from end-diastole to peak (-)dP/dt decreased by 7.5 +/- 2.3% at low, 4.4 +/- 2.2% at mid, and 1.9 +/- 1.6% at high LVEDP (p < 0.001). In protocol B (n = 7), LV inotropic state was altered by slow intravenous infusion of low-dose calcium. The ultrasound probe was activated before and after calcium. Effects of ultrasound were less pronounced after calcium. Time from end-diastole to peak (-)dP/dt decreased by 8.4 +/- 3.1% at baseline and by 3.5 +/- 2.1% after calcium (p < 0.001). In protocol C (n = 7), activation of the ultrasound probe was performed at baseline and after mild selective alpha 1-adrenergic stimulation (propranolol plus phenylephrine). Effects of ultrasound were similar at baseline and after propranolol but increased after phenylephrine . Time from end-diastole to peak (-)dP/dt decreased by 5.2 +/- 2.4% at baseline, by 5.3 +/- 1.9% after propranolol, and by 8.9 +/- 3.2% after phenylephrine (p < 0.05). ### conclusions Effects of intracavitary ultrasound, which are presumably mediated through modulation of endocardial endothelial function, were more important at low volume, lower calcium, and under mild selective alpha 1-adrenergic stimulation.

https://pubmed.ncbi.nlm.nih.gov/7681734/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Alteration of left ventricular endocardial function by intracavitary high-power ultrasound interacts with volume, inotropic state, and alpha 1-adrenergic stimulation. High-power intracavitary ultrasound abbreviates left ventricular (LV) ejection duration, thereby decreasing mechanical LV performance, presumably by selective impairment of endocardial endothelial function. ### Methods And Results Effects of ultrasound were evaluated in the ejecting LV of anesthetized, open-chest dogs under different conditions of LV volume and contractile state and after mild selective alpha 1-adrenergic stimulation. LV pressures, left atrial pressures, and regional segment lengths were measured in anterior and posterior midwall. A cylindrical ultrasound probe (0.9 MHz, 25 W) mounted on a catheter was inserted into the LV cavity through the apex and was activated for 4 minutes in each condition. In protocol A (n = 7), LV volume was altered with caval vein occlusion and intravenous dextran infusion. The ultrasound probe was activated at low (4.1 +/- 0.9 mm Hg), mid (10.6 +/- 1.5 mm Hg), and high (17.9 +/- 1.8 mm Hg) LV end-diastolic pressure (EDP). Effects of ultrasound were less pronounced at higher EDP. For example, the time interval from end-diastole to peak (-)dP/dt decreased by 7.5 +/- 2.3% at low, 4.4 +/- 2.2% at mid, and 1.9 +/- 1.6% at high LVEDP (p < 0.001). In protocol B (n = 7), LV inotropic state was altered by slow intravenous infusion of low-dose calcium. The ultrasound probe was activated before and after calcium. Effects of ultrasound were less pronounced after calcium. Time from end-diastole to peak (-)dP/dt decreased by 8.4 +/- 3.1% at baseline and by 3.5 +/- 2.1% after calcium (p < 0.001). In protocol C (n = 7), activation of the ultrasound probe was performed at baseline and after mild selective alpha 1-adrenergic stimulation (propranolol plus phenylephrine). Effects of ultrasound were similar at baseline and after propranolol but increased after phenylephrine . Time from end-diastole to peak (-)dP/dt decreased by 5.2 +/- 2.4% at baseline, by 5.3 +/- 1.9% after propranolol, and by 8.9 +/- 3.2% after phenylephrine (p < 0.05). ### conclusions Effects of intracavitary ultrasound, which are presumably mediated through modulation of endocardial endothelial function, were more important at low volume, lower calcium, and under mild selective alpha 1-adrenergic stimulation. ### Response: propranolol, phenylephrine

e164b14965950212d9af8afd0dc70c96

Thirty-four patients ( 4 patients with stage IIIb , 30 patients in stage IV ) , with median age 66 and performance status 0 - 1 , were administered paclitaxel , 175 mg/m(2 ) in a 3-h infusion rate on day 1 and vinorelbine , 25 mg/m(2 ) in a 10-min infusion rate on days 1 , and 8 with G-CSF and EPO support .

A phase II study of non-platinum based chemotherapy with paclitaxel and vinorelbine in non-small cell lung cancer. paclitaxel and vinorelbine combination in previous untreated patients with stage IIIb-IV non-small cell lung cancer (NSCLC) as a phase II study. ### Patients And Methods Thirty-four patients ( 4 patients with stage IIIb , 30 patients in stage IV ) , with median age 66 and performance status 0 - 1 , were administered paclitaxel , 175 mg/m(2 ) in a 3-h infusion rate on day 1 and vinorelbine , 25 mg/m(2 ) in a 10-min infusion rate on days 1 , and 8 with G-CSF and EPO support . ### results Among our 33 evaluable patients for toxicity 16 patients (48.4%) presented leukopenia and 15 patients (45.4%) presented anemia despite G-CSF and EPO administration. Two patients (6%) presented Grade III-IV peripheral neuropathy. The overall response rate was 67.7%; 5 patients (16.1%) showed complete response (2 patients stage IIIb) and 16 patients (51.6%) showed partial response (1 patient stage IIIb). The overall median survival time was 10 months (range 3-18 months) and the median disease-free survival was 9 months (range 3-15 months) with an 1-year survival time of 45.1% (14 patients). ### conclusion The results of the combination as 1st line treatment for patients with non-operable NSCLC are promising and should be further investigated.

https://pubmed.ncbi.nlm.nih.gov/12399133/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: A phase II study of non-platinum based chemotherapy with paclitaxel and vinorelbine in non-small cell lung cancer. paclitaxel and vinorelbine combination in previous untreated patients with stage IIIb-IV non-small cell lung cancer (NSCLC) as a phase II study. ### Patients And Methods Thirty-four patients ( 4 patients with stage IIIb , 30 patients in stage IV ) , with median age 66 and performance status 0 - 1 , were administered paclitaxel , 175 mg/m(2 ) in a 3-h infusion rate on day 1 and vinorelbine , 25 mg/m(2 ) in a 10-min infusion rate on days 1 , and 8 with G-CSF and EPO support . ### results Among our 33 evaluable patients for toxicity 16 patients (48.4%) presented leukopenia and 15 patients (45.4%) presented anemia despite G-CSF and EPO administration. Two patients (6%) presented Grade III-IV peripheral neuropathy. The overall response rate was 67.7%; 5 patients (16.1%) showed complete response (2 patients stage IIIb) and 16 patients (51.6%) showed partial response (1 patient stage IIIb). The overall median survival time was 10 months (range 3-18 months) and the median disease-free survival was 9 months (range 3-15 months) with an 1-year survival time of 45.1% (14 patients). ### conclusion The results of the combination as 1st line treatment for patients with non-operable NSCLC are promising and should be further investigated. ### Response: paclitaxel, vinorelbine

f34bb0d6ddd6e05d3a7d9a2cac06618f

Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia .

Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia . To determine an optimal biologic dose (OBD) of decitabine as a single agent and then the maximum-tolerated dose (MTD) of valproic acid (VA) combined with decitabine in acute myeloid leukemia (AML). ### Patients And Methods Twenty-five patients (median age, 70 years) were enrolled; 12 were untreated and 13 had relapsed AML. To determine an OBD (based on a gene re-expression end point), 14 patients received decitabine alone for 10 days. To determine the MTD, 11 patients received decitabine (at OBD, days 1 through 10) plus dose-escalating VA (days 5 through 21). ### results The OBD of decitabine was 20 mg/m(2)/d intravenously, with limited nonhematologic toxicity. In patients treated with decitabine plus VA, dose-limiting encephalopathy occurred in two of two patients at VA 25 mg/kg/d and one of six patients at VA 20 mg/kg/d. Drug-induced re-expression of estrogen receptor (ER) was associated with clinical response (P < or = .05). ER promoter demethylation, global DNA hypomethylation, depletion of DNA methyltransferase enzyme, and histone hyperacetylation were also observed. In an intent-to-treat analysis, the response rate was 44% (11 of 25). Of 21 assessable patients, 11 (52%) responded: four with morphologic and cytogenetic complete remission (CR; each had complex karyotype), four with incomplete CR, and three with partial remission. In untreated AML, four of nine assessable patients achieved CR. Clinical responses appeared similar for decitabine alone or with VA. ### conclusion Low-dose decitabine was safe and showed encouraging clinical and biologic activity in AML, but the addition of VA led to encephalopathy at relatively low doses. On the basis of these results, additional studies of decitabine (20 mg/m(2)/d for 10 days) alone or with an alternative deacetylating agent are warranted.

https://pubmed.ncbi.nlm.nih.gov/17679729/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia . To determine an optimal biologic dose (OBD) of decitabine as a single agent and then the maximum-tolerated dose (MTD) of valproic acid (VA) combined with decitabine in acute myeloid leukemia (AML). ### Patients And Methods Twenty-five patients (median age, 70 years) were enrolled; 12 were untreated and 13 had relapsed AML. To determine an OBD (based on a gene re-expression end point), 14 patients received decitabine alone for 10 days. To determine the MTD, 11 patients received decitabine (at OBD, days 1 through 10) plus dose-escalating VA (days 5 through 21). ### results The OBD of decitabine was 20 mg/m(2)/d intravenously, with limited nonhematologic toxicity. In patients treated with decitabine plus VA, dose-limiting encephalopathy occurred in two of two patients at VA 25 mg/kg/d and one of six patients at VA 20 mg/kg/d. Drug-induced re-expression of estrogen receptor (ER) was associated with clinical response (P < or = .05). ER promoter demethylation, global DNA hypomethylation, depletion of DNA methyltransferase enzyme, and histone hyperacetylation were also observed. In an intent-to-treat analysis, the response rate was 44% (11 of 25). Of 21 assessable patients, 11 (52%) responded: four with morphologic and cytogenetic complete remission (CR; each had complex karyotype), four with incomplete CR, and three with partial remission. In untreated AML, four of nine assessable patients achieved CR. Clinical responses appeared similar for decitabine alone or with VA. ### conclusion Low-dose decitabine was safe and showed encouraging clinical and biologic activity in AML, but the addition of VA led to encephalopathy at relatively low doses. On the basis of these results, additional studies of decitabine (20 mg/m(2)/d for 10 days) alone or with an alternative deacetylating agent are warranted. ### Response: decitabine, valproic

324a822968415251d1110100374543de

Early discontinuation of clopidogrel results in a transient rebound increase in risk of recurrence in acute coronary syndromes , but there are no published data on any similar rebound effect in patients with TIA or stroke that might inform the design of clinical trials of aspirin and clopidogrel in the acute phase .

Low risk of rebound events after a short course of clopidogrel in acute TIA or minor stroke. The combination of aspirin and clopidogrel is indicated after acute coronary events and possibly for a short period after TIA or minor ischemic stroke. Early discontinuation of clopidogrel results in a transient rebound increase in risk of recurrence in acute coronary syndromes , but there are no published data on any similar rebound effect in patients with TIA or stroke that might inform the design of clinical trials of aspirin and clopidogrel in the acute phase . ### methods A 30-day course of aspirin and clopidogrel (both 75 mg daily) was given to high-risk patients with TIA or minor ischemic stroke seen acutely in the EXPRESS study clinic from April 1, 2002, to March 31, 2009. clopidogrel was stopped after 30 days and aspirin continued. Recurrent events were ascertained at face-to-face follow-up. ### results A total of 320 patients were prescribed a 30-day course of aspirin and clopidogrel acutely after TIA or minor stroke. There were 5 recurrent ischemic strokes and 7 TIAs during the aspirin and clopidogrel treatment period, but no strokes and 4 TIAs during the 30 days after stopping clopidogrel. A similar temporal trend in stroke risk was seen in the 487 patients prescribed aspirin alone in the acute phase, with 12 and 5 strokes in the equivalent time periods. The upper 95% confidence intervals of the observed 0% risk of stroke during the 30 days after stopping clopidogrel was 1.15% overall. ### conclusion Although larger studies are required, our findings suggest there is unlikely to be a large rebound effect after discontinuation of a 30-day course of clopidogrel in acute TIA and minor ischemic stroke. However, planned trials of aspirin and clopidogrel in the acute phase after TIA or stroke should still follow-up beyond the cessation of clopidogrel treatment.

https://pubmed.ncbi.nlm.nih.gov/20530325/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Low risk of rebound events after a short course of clopidogrel in acute TIA or minor stroke. The combination of aspirin and clopidogrel is indicated after acute coronary events and possibly for a short period after TIA or minor ischemic stroke. Early discontinuation of clopidogrel results in a transient rebound increase in risk of recurrence in acute coronary syndromes , but there are no published data on any similar rebound effect in patients with TIA or stroke that might inform the design of clinical trials of aspirin and clopidogrel in the acute phase . ### methods A 30-day course of aspirin and clopidogrel (both 75 mg daily) was given to high-risk patients with TIA or minor ischemic stroke seen acutely in the EXPRESS study clinic from April 1, 2002, to March 31, 2009. clopidogrel was stopped after 30 days and aspirin continued. Recurrent events were ascertained at face-to-face follow-up. ### results A total of 320 patients were prescribed a 30-day course of aspirin and clopidogrel acutely after TIA or minor stroke. There were 5 recurrent ischemic strokes and 7 TIAs during the aspirin and clopidogrel treatment period, but no strokes and 4 TIAs during the 30 days after stopping clopidogrel. A similar temporal trend in stroke risk was seen in the 487 patients prescribed aspirin alone in the acute phase, with 12 and 5 strokes in the equivalent time periods. The upper 95% confidence intervals of the observed 0% risk of stroke during the 30 days after stopping clopidogrel was 1.15% overall. ### conclusion Although larger studies are required, our findings suggest there is unlikely to be a large rebound effect after discontinuation of a 30-day course of clopidogrel in acute TIA and minor ischemic stroke. However, planned trials of aspirin and clopidogrel in the acute phase after TIA or stroke should still follow-up beyond the cessation of clopidogrel treatment. ### Response: clopidogrel, aspirin, clopidogrel

e168784c0e299ecd1e3b2e48bfe61993

Patients received docetaxel 35 mg/m(2 ) and irinotecan 60 mg/m(2 ) , intravenously , on Days 1 and 8 , every 21 days , until disease progression .

Docetaxel and irinotecan in recurrent or metastatic head and neck cancer: a phase 2 trial of the Eastern Cooperative Oncology Group. docetaxel and irinotecan have single-agent antitumor activity in squamous cell carcinoma of the head and neck (SCCHN). The authors sought to evaluate their combination in the treatment of patients with recurrent or metastatic SCCHN. ### methods Eligibility criteria included recurrent or metastatic SCCHN with measurable disease, good performance status, and adequate laboratory parameters. Patients received docetaxel 35 mg/m(2 ) and irinotecan 60 mg/m(2 ) , intravenously , on Days 1 and 8 , every 21 days , until disease progression . The authors assessed UGT1A1 genotype, vascular endothelial growth factor (VEGF) in serum, and cyclooxygenase-2 and VEGF in baseline tumor tissue. ### results Fifty-two patients were analyzable: 20 chemotherapy naive (Group A) and 32 previously treated with 1 chemotherapy regimen (Group B); 73% of patients had distant metastasis, and 60% were paclitaxel-exposed. In Group A, 3 (15%) patients achieved a partial response; in Group B, 1 (3%) patient achieved a partial response. Median progression-free survival (PFS) and overall survival were 3.3 and 8.2 months in Group A and 1.9 and 5.0 months in Group B, respectively. Common serious toxicities were diarrhea, fatigue, and anorexia. Patients with high serum VEGF had a median PFS of 2.8 months versus 1.7 months for patients with low VEGF (P = .085). ### conclusions docetaxel and irinotecan had acceptable toxicities, but efficacy results in unselected patients with recurrent or metastatic SCCHN did not suggest an advantage over docetaxel alone or platinum-based regimens.

https://pubmed.ncbi.nlm.nih.gov/19634157/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Docetaxel and irinotecan in recurrent or metastatic head and neck cancer: a phase 2 trial of the Eastern Cooperative Oncology Group. docetaxel and irinotecan have single-agent antitumor activity in squamous cell carcinoma of the head and neck (SCCHN). The authors sought to evaluate their combination in the treatment of patients with recurrent or metastatic SCCHN. ### methods Eligibility criteria included recurrent or metastatic SCCHN with measurable disease, good performance status, and adequate laboratory parameters. Patients received docetaxel 35 mg/m(2 ) and irinotecan 60 mg/m(2 ) , intravenously , on Days 1 and 8 , every 21 days , until disease progression . The authors assessed UGT1A1 genotype, vascular endothelial growth factor (VEGF) in serum, and cyclooxygenase-2 and VEGF in baseline tumor tissue. ### results Fifty-two patients were analyzable: 20 chemotherapy naive (Group A) and 32 previously treated with 1 chemotherapy regimen (Group B); 73% of patients had distant metastasis, and 60% were paclitaxel-exposed. In Group A, 3 (15%) patients achieved a partial response; in Group B, 1 (3%) patient achieved a partial response. Median progression-free survival (PFS) and overall survival were 3.3 and 8.2 months in Group A and 1.9 and 5.0 months in Group B, respectively. Common serious toxicities were diarrhea, fatigue, and anorexia. Patients with high serum VEGF had a median PFS of 2.8 months versus 1.7 months for patients with low VEGF (P = .085). ### conclusions docetaxel and irinotecan had acceptable toxicities, but efficacy results in unselected patients with recurrent or metastatic SCCHN did not suggest an advantage over docetaxel alone or platinum-based regimens. ### Response: docetaxel, irinotecan

c00ca372934cc418ceb8a2e859b60fbe

Most patients with advanced ovarian cancer achieve a clinical complete remission following cytoreductive surgery and chemotherapy with paclitaxel plus carboplatin .

Gemcitabine and carboplatin in second-line ovarian cancer. Most patients with advanced ovarian cancer achieve a clinical complete remission following cytoreductive surgery and chemotherapy with paclitaxel plus carboplatin . However, a majority of these patients will ultimately recur, and second-line treatment for this group of patients is an important aspect of management of this disease as well as an area of active clinical investigation. Until recently, for patients with platinum-sensitive ovarian cancer (more than 6-month disease-free interval), chemotherapy with single-agent carboplatin was frequently recommended. However, two recent prospective randomized trials have shown that combination chemotherapy produces higher response rates and improvement in progression-free survival compared with treatment with single-agent carboplatin. One trial compared treatment with paclitaxel plus a platinum compound with re-treatment with platinum, and a second trial compared carboplatin plus gemcitabine re-treatment against carboplatin in patients with platinum-sensitive recurrent ovarian cancer. Both trials showed a 3-month improvement in progression-free survival in patients treated with the combination, as well as acceptable toxicity. In the absence of a prospective randomized trial comparing these two regimens in patients with platinum-sensitive recurrent ovarian cancer, the choice of which combination to use may depend on toxicity considerations.

https://pubmed.ncbi.nlm.nih.gov/16143161/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Gemcitabine and carboplatin in second-line ovarian cancer. Most patients with advanced ovarian cancer achieve a clinical complete remission following cytoreductive surgery and chemotherapy with paclitaxel plus carboplatin . However, a majority of these patients will ultimately recur, and second-line treatment for this group of patients is an important aspect of management of this disease as well as an area of active clinical investigation. Until recently, for patients with platinum-sensitive ovarian cancer (more than 6-month disease-free interval), chemotherapy with single-agent carboplatin was frequently recommended. However, two recent prospective randomized trials have shown that combination chemotherapy produces higher response rates and improvement in progression-free survival compared with treatment with single-agent carboplatin. One trial compared treatment with paclitaxel plus a platinum compound with re-treatment with platinum, and a second trial compared carboplatin plus gemcitabine re-treatment against carboplatin in patients with platinum-sensitive recurrent ovarian cancer. Both trials showed a 3-month improvement in progression-free survival in patients treated with the combination, as well as acceptable toxicity. In the absence of a prospective randomized trial comparing these two regimens in patients with platinum-sensitive recurrent ovarian cancer, the choice of which combination to use may depend on toxicity considerations. ### Response: paclitaxel, carboplatin

457f957cafaf7d707f008bebb67491e7

Patients were assigned to receive either oxaliplatin ( 100 mg/m(2 ) ) in the SOX arm or docetaxel ( 40 mg/m(2 ) ) in the mDS arm on day 1 of every 3-week cycle .

Low-dosed docetaxel showed equivalent efficacy but improved tolerability compared with oxaliplatin in the S-1-based first-line chemotherapy regimen for metastatic or recurrent gastric adenocarcinoma. Platinum-fluoropyrimidine combinations are the preferred first-line options for advanced gastric cancer (AGC) in East Asia. On the other hand, docetaxel-containing regimens without platinum have demonstrated promising activity in AGC. However, dose-related toxicity of docetaxel has limited its clinical adoption. This study compared the efficacy and safety of a modified low-dosed docetaxel plus S-1 (mDS) with oxaliplatin plus S-1 (SOX) in Chinese patients with AGC. Patients were assigned to receive either oxaliplatin ( 100 mg/m(2 ) ) in the SOX arm or docetaxel ( 40 mg/m(2 ) ) in the mDS arm on day 1 of every 3-week cycle . S-1 80-120 mg/day was administered orally on days 1-14 in the 3-week cycle in both groups. One hundred and eighty-eight patients (mDS regimen 101; SOX 87) showed similar overall survival (OS; 13.1 vs 12.8 months, P = 0.878), progression-free survival (PFS; 5.8 vs 5.5 months, P = 0.924), and overall response rate (39.7 vs 44.2%, P = 0.569) in the mDS and SOX arms, respectively. mDS was associated with significantly less grade 3/4 toxicities in thrombocytopenia (5.9 vs 16.1%) and gastrointestinal disturbances (1.0 vs 8.0%). Furthermore, in patients who had ever received oxaliplatin-based adjuvant chemotherapy (N = 40), mDS resulted in significantly superior OS (17.8 vs 9.5 months, P = 0.015) and PFS (7.0 vs 4.2 months, P = 0.008) compared with SOX. In conclusion, mDS was as effective as SOX in Chinese patients with AGC, but it resulted in a significantly improved tolerability. In patients who received oxaliplatin-based adjuvant chemotherapy before, mDS was associated with improved efficacy in the first-line setting.

https://pubmed.ncbi.nlm.nih.gov/26268397/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Low-dosed docetaxel showed equivalent efficacy but improved tolerability compared with oxaliplatin in the S-1-based first-line chemotherapy regimen for metastatic or recurrent gastric adenocarcinoma. Platinum-fluoropyrimidine combinations are the preferred first-line options for advanced gastric cancer (AGC) in East Asia. On the other hand, docetaxel-containing regimens without platinum have demonstrated promising activity in AGC. However, dose-related toxicity of docetaxel has limited its clinical adoption. This study compared the efficacy and safety of a modified low-dosed docetaxel plus S-1 (mDS) with oxaliplatin plus S-1 (SOX) in Chinese patients with AGC. Patients were assigned to receive either oxaliplatin ( 100 mg/m(2 ) ) in the SOX arm or docetaxel ( 40 mg/m(2 ) ) in the mDS arm on day 1 of every 3-week cycle . S-1 80-120 mg/day was administered orally on days 1-14 in the 3-week cycle in both groups. One hundred and eighty-eight patients (mDS regimen 101; SOX 87) showed similar overall survival (OS; 13.1 vs 12.8 months, P = 0.878), progression-free survival (PFS; 5.8 vs 5.5 months, P = 0.924), and overall response rate (39.7 vs 44.2%, P = 0.569) in the mDS and SOX arms, respectively. mDS was associated with significantly less grade 3/4 toxicities in thrombocytopenia (5.9 vs 16.1%) and gastrointestinal disturbances (1.0 vs 8.0%). Furthermore, in patients who had ever received oxaliplatin-based adjuvant chemotherapy (N = 40), mDS resulted in significantly superior OS (17.8 vs 9.5 months, P = 0.015) and PFS (7.0 vs 4.2 months, P = 0.008) compared with SOX. In conclusion, mDS was as effective as SOX in Chinese patients with AGC, but it resulted in a significantly improved tolerability. In patients who received oxaliplatin-based adjuvant chemotherapy before, mDS was associated with improved efficacy in the first-line setting. ### Response: oxaliplatin, docetaxel

21f9362aa253d6a8783dfec4552cd563

Agents in clinical trials for subsets of MDS include luspatercept , antibodies targeting CD33 , isocitrate dehydrogenase inhibitors , deacetylase inhibitors , venetoclax , and immunotherapies designed to overcome immune checkpoint inhibition .

Recent advances in the cellular and molecular understanding of myelodysplastic syndromes: implications for new therapeutic approaches. It has been more than 10 years since any new disease-modifying therapies have received regulatory approval for indications related to myelodysplastic syndromes (MDS). Advances in our collective biological understanding of MDS in the last decade, however, have made it possible to hope that effective therapeutics can be designed to improve MDS-associated cytopenias and patients' quality of life, and perhaps even delay clonal progression and extend survival. Classes of MDS-associated mutations and disordered biological pathways targeted by developmental therapeutics include the following: aberrant messenger RNA splicing, neomorphic enzymes in the citric acid cycle with oncogenic activity, overactivated tyrosine and serine-threonine kinases, epigenetic and chromatin remodeling alterations, abnormal telomere dynamics, and failed protection of DNA integrity. At present, treatments for MDS are usually administered as sequential monotherapy, but there is a trend toward clinical trials of combination therapies-in which new agents are added to a DNA hypomethylating agent backbone-for both upfront treatment and the treatment of relapsed/refractory disease. Agents in clinical trials for subsets of MDS include luspatercept , antibodies targeting CD33 , isocitrate dehydrogenase inhibitors , deacetylase inhibitors , venetoclax , and immunotherapies designed to overcome immune checkpoint inhibition . These biologically based therapeutics, as well as the encouraging precedent of 7 new approvals by the US Food and Drug Administration in 2017 for the treatment of acute leukemia, offer the prospect that 10 more years will not elapse before another new therapy is approved for MDS.

https://pubmed.ncbi.nlm.nih.gov/29741506/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Recent advances in the cellular and molecular understanding of myelodysplastic syndromes: implications for new therapeutic approaches. It has been more than 10 years since any new disease-modifying therapies have received regulatory approval for indications related to myelodysplastic syndromes (MDS). Advances in our collective biological understanding of MDS in the last decade, however, have made it possible to hope that effective therapeutics can be designed to improve MDS-associated cytopenias and patients' quality of life, and perhaps even delay clonal progression and extend survival. Classes of MDS-associated mutations and disordered biological pathways targeted by developmental therapeutics include the following: aberrant messenger RNA splicing, neomorphic enzymes in the citric acid cycle with oncogenic activity, overactivated tyrosine and serine-threonine kinases, epigenetic and chromatin remodeling alterations, abnormal telomere dynamics, and failed protection of DNA integrity. At present, treatments for MDS are usually administered as sequential monotherapy, but there is a trend toward clinical trials of combination therapies-in which new agents are added to a DNA hypomethylating agent backbone-for both upfront treatment and the treatment of relapsed/refractory disease. Agents in clinical trials for subsets of MDS include luspatercept , antibodies targeting CD33 , isocitrate dehydrogenase inhibitors , deacetylase inhibitors , venetoclax , and immunotherapies designed to overcome immune checkpoint inhibition . These biologically based therapeutics, as well as the encouraging precedent of 7 new approvals by the US Food and Drug Administration in 2017 for the treatment of acute leukemia, offer the prospect that 10 more years will not elapse before another new therapy is approved for MDS. ### Response: luspatercept, venetoclax

ebd455680a4ddeb606e9c2b94cd162c3

Possible differences between enalapril and captopril .

Possible differences between enalapril and captopril . Inhibitors of angiotensin converting enzyme block the conversion of angiotensin I to angiotensin II, the active hormone of the renin-angiotensin system. This inhibition leads to a reduction in angiotensin-mediated vasoconstriction and aldosterone production. Although converting enzyme inhibitors have other potential metabolic effects, their beneficial effects in hypertension and congestive heart failure appear to be, in large part, related to their ability to reduce angiotensin II. This causes an increase in plasma renin levels and a fall in plasma and urine aldosterone, which can be sustained for many years. As a consequence, converting enzyme inhibitors produce mild natriuresis and positive potassium balance. At conventionally used doses, enalapril more completely prevents posture-induced increases in aldosterone than does captopril, probably reflecting more complete inhibition of angiotensin II formation in vivo.

https://pubmed.ncbi.nlm.nih.gov/6089554/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Possible differences between enalapril and captopril . Inhibitors of angiotensin converting enzyme block the conversion of angiotensin I to angiotensin II, the active hormone of the renin-angiotensin system. This inhibition leads to a reduction in angiotensin-mediated vasoconstriction and aldosterone production. Although converting enzyme inhibitors have other potential metabolic effects, their beneficial effects in hypertension and congestive heart failure appear to be, in large part, related to their ability to reduce angiotensin II. This causes an increase in plasma renin levels and a fall in plasma and urine aldosterone, which can be sustained for many years. As a consequence, converting enzyme inhibitors produce mild natriuresis and positive potassium balance. At conventionally used doses, enalapril more completely prevents posture-induced increases in aldosterone than does captopril, probably reflecting more complete inhibition of angiotensin II formation in vivo. ### Response: enalapril, captopril

e4fd3f4f3543e792ba43e968cecc17af

Exposure of the saphenous veins to imipenem or imipenem combined with amphotericin B had no adverse effects on the viability of the endothelial cells with 12 h exposure .

Effects of antibiotics on the endothelium of fresh and cryopreserved canine saphenous veins. To determine if antibiotic solutions for potential use in antimicrobial treatment of tissues were detrimental to cell viability, canine saphenous veins were exposed to three different antibiotic solutions at 37 degrees C for 12 h. Viability was determined by tissue culture, utilizing a limiting dilution assay. The antibiotic series included two formulations currently used for the preservation of heart valves and a new formulation containing imipenem, a broad spectrum beta-lactam. Currently used antibiotic regimes and imipenem with gentamicin resulted in a decrease of 30 to 50% of the viable endothelial cells within 12 h. Exposure of the saphenous veins to imipenem or imipenem combined with amphotericin B had no adverse effects on the viability of the endothelial cells with 12 h exposure . However, veins exposed to amphotericin B were more susceptible to subsequent damage during freezing and thawing than veins frozen after incubation with either imipenem alone or imipenem combined with flucytosine. These studies indicate that imipenem combined with flucytosine is suitable for use with vein grafts.

https://pubmed.ncbi.nlm.nih.gov/8319486/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Effects of antibiotics on the endothelium of fresh and cryopreserved canine saphenous veins. To determine if antibiotic solutions for potential use in antimicrobial treatment of tissues were detrimental to cell viability, canine saphenous veins were exposed to three different antibiotic solutions at 37 degrees C for 12 h. Viability was determined by tissue culture, utilizing a limiting dilution assay. The antibiotic series included two formulations currently used for the preservation of heart valves and a new formulation containing imipenem, a broad spectrum beta-lactam. Currently used antibiotic regimes and imipenem with gentamicin resulted in a decrease of 30 to 50% of the viable endothelial cells within 12 h. Exposure of the saphenous veins to imipenem or imipenem combined with amphotericin B had no adverse effects on the viability of the endothelial cells with 12 h exposure . However, veins exposed to amphotericin B were more susceptible to subsequent damage during freezing and thawing than veins frozen after incubation with either imipenem alone or imipenem combined with flucytosine. These studies indicate that imipenem combined with flucytosine is suitable for use with vein grafts. ### Response: imipenem, imipenem, amphotericin

22e4c43526214a50dd7ba189ee96a40d

First-line chemotherapy was either R-CHOP ( rituximab , cyclophosphamide , doxorubicin , vincristine and prednisolone ) or CHOP-like-based regimen .

[Primary testicular non-Hodgkin's lymphoma: clinical analysis of 21 cases]. To explore the clinical characteristics and prognosis of patients with primary testicular non-Hodgkin's lymphoma. ### methods The clinical profiles and prognostic factors of 21 cases newly diagnosed as primary testicular non-Hodgkin's lymphoma at Peking University Cancer Hospital from January 2005 to December 2012 were retrospectively analyzed. ### results Their median age was 59 (34-86) years. And they were classified as Ann Arbor stage I (n = 8), stage II (n = 2) and stage IV (n = 11). There were B symptoms (n = 4), extranodal involvement outside testis (n = 12) and elevated lactate dehydrogenase (LDH) at diagnosis (n = 6). The scores of international prognostic index (IPI) were 0-1 point (n = 10), 3 points (n = 10) and 4 points (n = 1). The regimens included orchidectomy as the initial treatment (n = 15), chemotherapy followed by radiotherapy (n = 7) and CNS prophylaxis during treatment (n = 15). All patients were pathologically diagnosed as diffuse large B-cell lymphoma. And 11 cases belonged to the non-germinal center B cell-like subgroup. First-line chemotherapy was either R-CHOP ( rituximab , cyclophosphamide , doxorubicin , vincristine and prednisolone ) or CHOP-like-based regimen . Complete response was achieved in 85.7% of patients. The median follow-up period was 18 (6-58) months. The 1, 2 and 3-year survival rates were 100%, 80% and 60% respectively. Statistical analysis showed that the first-line chemotherapy with rituximab was a prognostic factor (P = 0.038).Other factors included stage (P = 0.275), LDH level (P = 0.179) , β2-microglobulin level (P = 0.229) and IPI (P = 0.275) . ### conclusions The prognosis of primary testicular non-Hodgkin's lymphoma is usually poor. The first-line chemotherapy with rituximab is a prognostic factor.

https://pubmed.ncbi.nlm.nih.gov/24169330/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: [Primary testicular non-Hodgkin's lymphoma: clinical analysis of 21 cases]. To explore the clinical characteristics and prognosis of patients with primary testicular non-Hodgkin's lymphoma. ### methods The clinical profiles and prognostic factors of 21 cases newly diagnosed as primary testicular non-Hodgkin's lymphoma at Peking University Cancer Hospital from January 2005 to December 2012 were retrospectively analyzed. ### results Their median age was 59 (34-86) years. And they were classified as Ann Arbor stage I (n = 8), stage II (n = 2) and stage IV (n = 11). There were B symptoms (n = 4), extranodal involvement outside testis (n = 12) and elevated lactate dehydrogenase (LDH) at diagnosis (n = 6). The scores of international prognostic index (IPI) were 0-1 point (n = 10), 3 points (n = 10) and 4 points (n = 1). The regimens included orchidectomy as the initial treatment (n = 15), chemotherapy followed by radiotherapy (n = 7) and CNS prophylaxis during treatment (n = 15). All patients were pathologically diagnosed as diffuse large B-cell lymphoma. And 11 cases belonged to the non-germinal center B cell-like subgroup. First-line chemotherapy was either R-CHOP ( rituximab , cyclophosphamide , doxorubicin , vincristine and prednisolone ) or CHOP-like-based regimen . Complete response was achieved in 85.7% of patients. The median follow-up period was 18 (6-58) months. The 1, 2 and 3-year survival rates were 100%, 80% and 60% respectively. Statistical analysis showed that the first-line chemotherapy with rituximab was a prognostic factor (P = 0.038).Other factors included stage (P = 0.275), LDH level (P = 0.179) , β2-microglobulin level (P = 0.229) and IPI (P = 0.275) . ### conclusions The prognosis of primary testicular non-Hodgkin's lymphoma is usually poor. The first-line chemotherapy with rituximab is a prognostic factor. ### Response: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone

cb3413a04ed145ab2ccfc3b8ba5675d8

The combination of rituximab with vincristine and 5-day cyclophosphamide is able to produce CR in patients with advanced follicular lymphoma , even in patients resistant to third-generation regimens .

Immunochemotherapy with rituximab, vincristine and 5-day cyclophosphamide for heavily pretreated follicular lymphoma. Therapeutic options for relapsed or refractory follicular lymphoma include combination chemotherapy, immunotherapy and, for selected patients, autotransplant. Because of the different mechanisms of action and non-overlapping toxicities, combination of rituximab with chemotherapy is a rational approach. ### methods 30 patients with follicular non-Hodgkin's lymphoma with advanced-stage disease were treated with four cycles of immunochemotherapy with rituximab 375 mg/m2 on day 1, vincristine 2 mg i.v. on day 2 and cyclophosphamide 400 mg/m2 i.v. from days 2 to 6, repeated at 3-week intervals. All patients had received multiple lines of therapy (median 3); 9 (30%) had relapses (2 after high-dose therapy with autologous transplant), and 21 (70%) were in relapse and refractory to salvage treatment (with an anthracycline-containing regimen in 19). ### results Of 29 patients evaluable for response, 16 (55 %) obtained a complete response (CR) and 3 (10%) a partial response (PR), with an overall response rate of 65% (19/29); 10 patients (35%) achieved less than PR. The median event-free survival was 16.1 months for all patients, being 22.8 months for responders. After a median follow-up of 2 years from the start of therapy (range 6 months to 3.8 years), of 16 patients who achieved CR, 10 remain free of disease. ### conclusion The combination of rituximab with vincristine and 5-day cyclophosphamide is able to produce CR in patients with advanced follicular lymphoma , even in patients resistant to third-generation regimens . The regimen designed on the basis of pharmacokinetics of the chimeric antibody seemed important for the clinical efficacy of the combination.

https://pubmed.ncbi.nlm.nih.gov/16006752/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Immunochemotherapy with rituximab, vincristine and 5-day cyclophosphamide for heavily pretreated follicular lymphoma. Therapeutic options for relapsed or refractory follicular lymphoma include combination chemotherapy, immunotherapy and, for selected patients, autotransplant. Because of the different mechanisms of action and non-overlapping toxicities, combination of rituximab with chemotherapy is a rational approach. ### methods 30 patients with follicular non-Hodgkin's lymphoma with advanced-stage disease were treated with four cycles of immunochemotherapy with rituximab 375 mg/m2 on day 1, vincristine 2 mg i.v. on day 2 and cyclophosphamide 400 mg/m2 i.v. from days 2 to 6, repeated at 3-week intervals. All patients had received multiple lines of therapy (median 3); 9 (30%) had relapses (2 after high-dose therapy with autologous transplant), and 21 (70%) were in relapse and refractory to salvage treatment (with an anthracycline-containing regimen in 19). ### results Of 29 patients evaluable for response, 16 (55 %) obtained a complete response (CR) and 3 (10%) a partial response (PR), with an overall response rate of 65% (19/29); 10 patients (35%) achieved less than PR. The median event-free survival was 16.1 months for all patients, being 22.8 months for responders. After a median follow-up of 2 years from the start of therapy (range 6 months to 3.8 years), of 16 patients who achieved CR, 10 remain free of disease. ### conclusion The combination of rituximab with vincristine and 5-day cyclophosphamide is able to produce CR in patients with advanced follicular lymphoma , even in patients resistant to third-generation regimens . The regimen designed on the basis of pharmacokinetics of the chimeric antibody seemed important for the clinical efficacy of the combination. ### Response: rituximab, vincristine, cyclophosphamide

989e4dbe95c2ec8043f087978dfa8204

The results showed that lamotrigine did not produce any change in cognitive function , while carbamazepine produced cognitive dysfunction .

Effect of carbamazepine and lamotrigine on cognitive function and oxidative stress in brain during chemical epileptogenesis in rats. The present study assessed the effect of carbamazepine and lamotrigine on cognitive function and oxidative stress in brain during chemically induced epileptogenesis in rats. Epileptogenesis was induced by administration of pentylenetetrazole (30 mg/kg, s.c.) on alternate days (three times/week) for 9-11 weeks or until stage 4 of seizure score was achieved. The neurobehavioural parameters used for cognitive assessment were step-down latency in continuous avoidance apparatus and transfer latency in elevated plus maze test paradigm. carbamazepine and lamotrigine were administered intraperitoneally in doses of 60 mg/kg and 25 mg/kg, respectively, according to the groups, once a day for 11 weeks. Oxidative stress was assessed in isolated homogenized whole brain samples and estimated for the levels of malondialdehyde, reduced glutathione, catalase and superoxide dismutase. The results showed that lamotrigine did not produce any change in cognitive function , while carbamazepine produced cognitive dysfunction . Cognitive decline seen in the carbamazepine-treated pentylenetetrazole-kindled group was also associated with increased oxidative stress. lamotrigine treatment had no effect on oxidative stress parameters alone, while it significantly decreased oxidative stress in the pentylenetetrazole-kindled group as compared to the pentylenetetrazole-kindled carbamazepine-treated group.

https://pubmed.ncbi.nlm.nih.gov/20002063/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Effect of carbamazepine and lamotrigine on cognitive function and oxidative stress in brain during chemical epileptogenesis in rats. The present study assessed the effect of carbamazepine and lamotrigine on cognitive function and oxidative stress in brain during chemically induced epileptogenesis in rats. Epileptogenesis was induced by administration of pentylenetetrazole (30 mg/kg, s.c.) on alternate days (three times/week) for 9-11 weeks or until stage 4 of seizure score was achieved. The neurobehavioural parameters used for cognitive assessment were step-down latency in continuous avoidance apparatus and transfer latency in elevated plus maze test paradigm. carbamazepine and lamotrigine were administered intraperitoneally in doses of 60 mg/kg and 25 mg/kg, respectively, according to the groups, once a day for 11 weeks. Oxidative stress was assessed in isolated homogenized whole brain samples and estimated for the levels of malondialdehyde, reduced glutathione, catalase and superoxide dismutase. The results showed that lamotrigine did not produce any change in cognitive function , while carbamazepine produced cognitive dysfunction . Cognitive decline seen in the carbamazepine-treated pentylenetetrazole-kindled group was also associated with increased oxidative stress. lamotrigine treatment had no effect on oxidative stress parameters alone, while it significantly decreased oxidative stress in the pentylenetetrazole-kindled group as compared to the pentylenetetrazole-kindled carbamazepine-treated group. ### Response: lamotrigine, carbamazepine

b0dcf3e3038370ed524af039d260b6ef

These results confirm that sequential decitabine and carboplatin requires further investigation as a combination treatment for melanoma .

Sequential decitabine and carboplatin treatment increases the DNA repair protein XPC, increases apoptosis and decreases proliferation in melanoma. Melanoma has two key features, an over-representation of UV-induced mutations and resistance to DNA damaging chemotherapy agents. Both of these features may result from dysfunction of the nucleotide excision repair pathway, in particular the DNA damage detection branch, global genome repair (GGR). The key GGR component XPC does not respond to DNA damage in melanoma, the cause of this lack of response has not been investigated. In this study, we investigated the role of methylation in reduced XPC in melanoma. ### methods To reduce methylation and induce DNA-damage, melanoma cell lines were treated with decitabine and carboplatin, individually and sequentially. Global DNA methylation levels, XPC mRNA and protein expression and methylation of the XPC promoter were examined. Apoptosis, cell proliferation and senescence were also quantified. XPC siRNA was used to determine that the responses seen were reliant on XPC induction. ### results Treatment with high-dose decitabine resulted in global demethylation, including the the shores of the XPC CpG island and significantly increased XPC mRNA expression. Lower, clinically relevant dose of decitabine also resulted in global demethylation including the CpG island shores and induced XPC in 50% of cell lines. decitabine followed by DNA-damaging carboplatin treatment led to significantly higher XPC expression in 75% of melanoma cell lines tested. Combined sequential treatment also resulted in a greater apoptotic response in 75% of cell lines compared to carboplatin alone, and significantly slowed cell proliferation, with some melanoma cell lines going into senescence. Inhibiting the increased XPC using siRNA had a small but significant negative effect, indicating that XPC plays a partial role in the response to sequential decitabine and carboplatin. ### conclusions Demethylation using decitabine increased XPC and apoptosis after sequential carboplatin. These results confirm that sequential decitabine and carboplatin requires further investigation as a combination treatment for melanoma .

https://pubmed.ncbi.nlm.nih.gov/29373959/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Sequential decitabine and carboplatin treatment increases the DNA repair protein XPC, increases apoptosis and decreases proliferation in melanoma. Melanoma has two key features, an over-representation of UV-induced mutations and resistance to DNA damaging chemotherapy agents. Both of these features may result from dysfunction of the nucleotide excision repair pathway, in particular the DNA damage detection branch, global genome repair (GGR). The key GGR component XPC does not respond to DNA damage in melanoma, the cause of this lack of response has not been investigated. In this study, we investigated the role of methylation in reduced XPC in melanoma. ### methods To reduce methylation and induce DNA-damage, melanoma cell lines were treated with decitabine and carboplatin, individually and sequentially. Global DNA methylation levels, XPC mRNA and protein expression and methylation of the XPC promoter were examined. Apoptosis, cell proliferation and senescence were also quantified. XPC siRNA was used to determine that the responses seen were reliant on XPC induction. ### results Treatment with high-dose decitabine resulted in global demethylation, including the the shores of the XPC CpG island and significantly increased XPC mRNA expression. Lower, clinically relevant dose of decitabine also resulted in global demethylation including the CpG island shores and induced XPC in 50% of cell lines. decitabine followed by DNA-damaging carboplatin treatment led to significantly higher XPC expression in 75% of melanoma cell lines tested. Combined sequential treatment also resulted in a greater apoptotic response in 75% of cell lines compared to carboplatin alone, and significantly slowed cell proliferation, with some melanoma cell lines going into senescence. Inhibiting the increased XPC using siRNA had a small but significant negative effect, indicating that XPC plays a partial role in the response to sequential decitabine and carboplatin. ### conclusions Demethylation using decitabine increased XPC and apoptosis after sequential carboplatin. These results confirm that sequential decitabine and carboplatin requires further investigation as a combination treatment for melanoma . ### Response: decitabine, carboplatin

08f60e955a6158992b104ff65ea478bd

[ Rhabdomyosarcoma of the urinary bladder : complete remission induced by vinblastine , cis-platinum , and bleomycin ] .

[ Rhabdomyosarcoma of the urinary bladder : complete remission induced by vinblastine , cis-platinum , and bleomycin ] . Combination therapy consisting of vincristine, actinomycin-D, and cyclophosphamide with or without adriamycin is the most common chemotherapy for rhabdomyosarcoma in childhood. But the effective chemotherapy for rhabdomyosarcoma resistant to these four drugs has not been established. We report a case with rhabdomyosarcoma, which was resistant to these four drugs but responded completely to three drug combination chemotherapy consisting of vinblastine, cis-platinum, and bleomycin (VPB therapy). A 11-months-old boy was referred to us because of giant abdominal tumor. Postoperative diagnosis was Group III embryonal rhabdomyosarcoma of the urinary bladder. Partial resection was followed by vincristine, actinomycin-D, cyclophosphamide, and adriamycin, but his residual tumor was growing. Then VPB therapy was administered and the first course of the chemotherapy reduced the size of tumor. After three courses of VPB therapy the second-look operation was performed. At operation no residual tumor was found and a complete remission was confirmed. During the course of VPB therapy no severe adverse effect was detectable.

https://pubmed.ncbi.nlm.nih.gov/6191695/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: [ Rhabdomyosarcoma of the urinary bladder : complete remission induced by vinblastine , cis-platinum , and bleomycin ] . Combination therapy consisting of vincristine, actinomycin-D, and cyclophosphamide with or without adriamycin is the most common chemotherapy for rhabdomyosarcoma in childhood. But the effective chemotherapy for rhabdomyosarcoma resistant to these four drugs has not been established. We report a case with rhabdomyosarcoma, which was resistant to these four drugs but responded completely to three drug combination chemotherapy consisting of vinblastine, cis-platinum, and bleomycin (VPB therapy). A 11-months-old boy was referred to us because of giant abdominal tumor. Postoperative diagnosis was Group III embryonal rhabdomyosarcoma of the urinary bladder. Partial resection was followed by vincristine, actinomycin-D, cyclophosphamide, and adriamycin, but his residual tumor was growing. Then VPB therapy was administered and the first course of the chemotherapy reduced the size of tumor. After three courses of VPB therapy the second-look operation was performed. At operation no residual tumor was found and a complete remission was confirmed. During the course of VPB therapy no severe adverse effect was detectable. ### Response: vinblastine, bleomycin, cis-platinum

a3728ecff22176b9a5c91cf433c52ad7

Recent comparative studies suggest that atenolol ( 200 mg daily ) , metoprolol ( 200 mg daily ) ; acebutolol ( 400 mg daily ) , oxprenolol ( 160 mg daily ) , nadolol ( 80 mg daily ) and timolol ( 20 mg daily ) produce a beneficial clinical response equal to that seen with propranolol ( 160 mg daily ) .

Use of beta-adrenoceptor blocking drugs in hyperthyroidism. There is an increasing use and variety of beta-adrenoceptor blocking agents (beta-blockers) available for the treatment of hyperthyroidism. Recent comparative studies suggest that atenolol ( 200 mg daily ) , metoprolol ( 200 mg daily ) ; acebutolol ( 400 mg daily ) , oxprenolol ( 160 mg daily ) , nadolol ( 80 mg daily ) and timolol ( 20 mg daily ) produce a beneficial clinical response equal to that seen with propranolol ( 160 mg daily ) . Most beta-blockers reduce resting heart rate by approximately 25 to 30 beats/min, although a lesser reduction is seen with those possessing intrinsic sympathomimetic activity such as oxprenolol and pindolol. While earlier studies employing large doses of intravenous propranolol concluded that beta-blockade reduced myocardial contractility, more recent non-invasive studies suggest that the predominant cardiac effect is on heart rate. In patients with cardiac failure, beta-blockers may, however, produce a profound fall in cardiac output. Nevertheless, in combination with digoxin they may be useful in controlling the atrial fibrillation of thyrocardiac disease. beta-Blockers improve nervousness and tremor (although to a lesser extent with cardioselective agents) and severe myopathy, and they also reduce the frequency of paralysis in patients with thyrotoxic periodic paralysis. There is often subjective improvement in sweating but usually no major effect on eye signs. Recent studies show a 10% reduction in oxygen consumption/basal metabolic rate with long term oral use of selective or nonselective beta-blockers. In addition, many agents (propranolol, metoprolol, nadolol and sotalol but not acebutolol, atenolol or oxprenolol) reduce circulating tri-iodothyronine (T3) concentration by between 10 and 40%, although the clinical significance of this effect (if any) is not established. beta-Blockers may also have endocrinological effects on gastrin, cyclic AMP, catecholamines and other hormone levels. Given in adequate dosage, propranolol has been shown to control thyrotoxic hypercalcaemia. Minor side effects (nausea, headaches, tiredness, etc.) are quite common but overall beta-blockers are well tolerated by the thyrotoxic patient. The major use of these drugs is in symptomatic control while awaiting definitive diagnosis or treatment. As an adjunct to antithyroid drugs or radioactive iodine, beta-blockers will produce a satisfactory clinical response in the weeks to months before these forms of therapy produce a euthyroid state. beta-Blockers are more convenient than antithyroid drugs in the control of patients receiving therapeutic radioiodine, in that continuous therapy and assessment of biochemical response is possible.(ABSTRACT TRUNCATED AT 400 WORDS)

https://pubmed.ncbi.nlm.nih.gov/6144501/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Use of beta-adrenoceptor blocking drugs in hyperthyroidism. There is an increasing use and variety of beta-adrenoceptor blocking agents (beta-blockers) available for the treatment of hyperthyroidism. Recent comparative studies suggest that atenolol ( 200 mg daily ) , metoprolol ( 200 mg daily ) ; acebutolol ( 400 mg daily ) , oxprenolol ( 160 mg daily ) , nadolol ( 80 mg daily ) and timolol ( 20 mg daily ) produce a beneficial clinical response equal to that seen with propranolol ( 160 mg daily ) . Most beta-blockers reduce resting heart rate by approximately 25 to 30 beats/min, although a lesser reduction is seen with those possessing intrinsic sympathomimetic activity such as oxprenolol and pindolol. While earlier studies employing large doses of intravenous propranolol concluded that beta-blockade reduced myocardial contractility, more recent non-invasive studies suggest that the predominant cardiac effect is on heart rate. In patients with cardiac failure, beta-blockers may, however, produce a profound fall in cardiac output. Nevertheless, in combination with digoxin they may be useful in controlling the atrial fibrillation of thyrocardiac disease. beta-Blockers improve nervousness and tremor (although to a lesser extent with cardioselective agents) and severe myopathy, and they also reduce the frequency of paralysis in patients with thyrotoxic periodic paralysis. There is often subjective improvement in sweating but usually no major effect on eye signs. Recent studies show a 10% reduction in oxygen consumption/basal metabolic rate with long term oral use of selective or nonselective beta-blockers. In addition, many agents (propranolol, metoprolol, nadolol and sotalol but not acebutolol, atenolol or oxprenolol) reduce circulating tri-iodothyronine (T3) concentration by between 10 and 40%, although the clinical significance of this effect (if any) is not established. beta-Blockers may also have endocrinological effects on gastrin, cyclic AMP, catecholamines and other hormone levels. Given in adequate dosage, propranolol has been shown to control thyrotoxic hypercalcaemia. Minor side effects (nausea, headaches, tiredness, etc.) are quite common but overall beta-blockers are well tolerated by the thyrotoxic patient. The major use of these drugs is in symptomatic control while awaiting definitive diagnosis or treatment. As an adjunct to antithyroid drugs or radioactive iodine, beta-blockers will produce a satisfactory clinical response in the weeks to months before these forms of therapy produce a euthyroid state. beta-Blockers are more convenient than antithyroid drugs in the control of patients receiving therapeutic radioiodine, in that continuous therapy and assessment of biochemical response is possible.(ABSTRACT TRUNCATED AT 400 WORDS) ### Response: atenolol, metoprolol, acebutolol, oxprenolol, nadolol, timolol, propranolol

6940b79498c210d4948acbca8b303f0c

All the animals in the placebo group had tumors in each lobe compared with only 43 % each in the dorsolateral ( DLP ) and anterior prostate ( AP ) of the animals treated with raloxifene ( 10 mg/kg/day ) plus nimesulide .

Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by raloxifene, an antiestrogen with anti-androgen action, but not nimesulide, a selective cyclooxygenase-2 inhibitor. The chemopreventive efficacies of raloxifene and nimesulide, an anti-estrogen but with anti-androgen action and a cyclooxygenase-2 (COX-2) selective inhibitor, respectively, were evaluated in probasin/SV40 T antigen (Tag) transgenic (TG) rats. The treatment groups were placebo, nimesulide (400 p.p.m. in basal diet p.o.), raloxifene (slow-release pellets implanted s.c., 5 mg/kg/day), raloxifene (5 mg/kg/day) plus nimesulide (400 p.p.m.), and raloxifene (10 mg/kg/day) plus nimesulide (400 p.p.m.). Animals were killed at 17 weeks of age, and prostate tissues were harvested and weighed by lobes. Tissues were evaluated by histology, immunohistochemistry, and western blot analyses and blood was collected to measure the testosterone levels. All the animals in the placebo group had tumors in each lobe compared with only 43 % each in the dorsolateral ( DLP ) and anterior prostate ( AP ) of the animals treated with raloxifene ( 10 mg/kg/day ) plus nimesulide . The total prostate weights and adenocarcinoma portions were significantly reduced in the three raloxifene-treated groups, whereas atrophic glands were increased. There were no significant differences between the nimesulide alone and placebo groups or between the raloxifene (5 mg/kg/day) alone and raloxifene (5 mg/kg/day) plus nimesulide group, suggesting a lack of cancer preventive effects of the COX-2 inhibitor in this animal model. PCNA positive rates in ventral prostate (VP) and DLP, and androgen receptor (AR) levels in VP were significantly reduced in the three raloxifene-treated groups. Furthermore, circulating testosterone was decreased after raloxifene (10 mg/kg/day) plus nimesulide treatment. These results demonstrate that raloxifene, but not nimesulide, inhibits prostate carcinogenesis in SV40 Tag TG rats associated with a decline in circulating testosterone levels and a loss of AR expression, as well as an inhibition of cell proliferation.

https://pubmed.ncbi.nlm.nih.gov/15731164/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by raloxifene, an antiestrogen with anti-androgen action, but not nimesulide, a selective cyclooxygenase-2 inhibitor. The chemopreventive efficacies of raloxifene and nimesulide, an anti-estrogen but with anti-androgen action and a cyclooxygenase-2 (COX-2) selective inhibitor, respectively, were evaluated in probasin/SV40 T antigen (Tag) transgenic (TG) rats. The treatment groups were placebo, nimesulide (400 p.p.m. in basal diet p.o.), raloxifene (slow-release pellets implanted s.c., 5 mg/kg/day), raloxifene (5 mg/kg/day) plus nimesulide (400 p.p.m.), and raloxifene (10 mg/kg/day) plus nimesulide (400 p.p.m.). Animals were killed at 17 weeks of age, and prostate tissues were harvested and weighed by lobes. Tissues were evaluated by histology, immunohistochemistry, and western blot analyses and blood was collected to measure the testosterone levels. All the animals in the placebo group had tumors in each lobe compared with only 43 % each in the dorsolateral ( DLP ) and anterior prostate ( AP ) of the animals treated with raloxifene ( 10 mg/kg/day ) plus nimesulide . The total prostate weights and adenocarcinoma portions were significantly reduced in the three raloxifene-treated groups, whereas atrophic glands were increased. There were no significant differences between the nimesulide alone and placebo groups or between the raloxifene (5 mg/kg/day) alone and raloxifene (5 mg/kg/day) plus nimesulide group, suggesting a lack of cancer preventive effects of the COX-2 inhibitor in this animal model. PCNA positive rates in ventral prostate (VP) and DLP, and androgen receptor (AR) levels in VP were significantly reduced in the three raloxifene-treated groups. Furthermore, circulating testosterone was decreased after raloxifene (10 mg/kg/day) plus nimesulide treatment. These results demonstrate that raloxifene, but not nimesulide, inhibits prostate carcinogenesis in SV40 Tag TG rats associated with a decline in circulating testosterone levels and a loss of AR expression, as well as an inhibition of cell proliferation. ### Response: raloxifene, nimesulide

c68e463583257ffddef0e7d4b4325724

Overdose of dolutegravir in combination with tenofovir disaproxil fumarate/emtricitabine in suicide attempt in a 21-year old patient .

Overdose of dolutegravir in combination with tenofovir disaproxil fumarate/emtricitabine in suicide attempt in a 21-year old patient . A 21 year old MSM patient with newly diagnosed HIV infection was hospitalized in our department after ingestion of an overdose of his antiretroviral therapy (ART) comprising dolutegravir (DTG - Tivicay®) and tenofovir disaproxil fumarate/emtricitabine (Truvada®) in suicidal intention. On admission, the patient did not show any clinical signs of intoxication and laboratory findings were unremarkable. After 6 hours of intensive care monitoring, the patient was referred to a psychiatric clinic. 5 days after the day of intoxication, serum creatinine levels increased to high normal values (1.2 mg/dl). However, levels never exceeded the upper threshold. 8 and 12 weeks later, serum creatinine normalized to levels measured prior to the intoxication. No other adverse events occurred, and the patient does not suffer from permanent impairments.

https://pubmed.ncbi.nlm.nih.gov/26045712/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Overdose of dolutegravir in combination with tenofovir disaproxil fumarate/emtricitabine in suicide attempt in a 21-year old patient . A 21 year old MSM patient with newly diagnosed HIV infection was hospitalized in our department after ingestion of an overdose of his antiretroviral therapy (ART) comprising dolutegravir (DTG - Tivicay®) and tenofovir disaproxil fumarate/emtricitabine (Truvada®) in suicidal intention. On admission, the patient did not show any clinical signs of intoxication and laboratory findings were unremarkable. After 6 hours of intensive care monitoring, the patient was referred to a psychiatric clinic. 5 days after the day of intoxication, serum creatinine levels increased to high normal values (1.2 mg/dl). However, levels never exceeded the upper threshold. 8 and 12 weeks later, serum creatinine normalized to levels measured prior to the intoxication. No other adverse events occurred, and the patient does not suffer from permanent impairments. ### Response: dolutegravir, tenofovir

e464e3850c3026b2c1eb5be706e579ad

Abiraterone acetate and prednisone in the pre- and post-docetaxel setting for metastatic castration-resistant prostate cancer : a mono-institutional experience focused on cardiovascular events and their impact on clinical outcomes .

Abiraterone acetate and prednisone in the pre- and post-docetaxel setting for metastatic castration-resistant prostate cancer : a mono-institutional experience focused on cardiovascular events and their impact on clinical outcomes . The aim of this work was to to evaluate the incidence and risk factors of adverse events (AEs), focusing on cardiovascular events (CVEs) and hypokalemia, in patients treated with abiraterone acetate (AA) and prednisone (PDN) outside clinical trials, and their association with survival outcomes. ### methods This was a retrospective cohort study of 105 patients treated from 2011 to 2016. Incidence of AEs was descriptively summarized in the whole cohort and by subgroup (pre- ### results Overall, median PFS and OS were 14.9 and 24.6 months, respectively. Prostate-specific antigen (PSA) ⩾ 10 ng/ml ( ### conclusions Median PFS and OS estimates and incidence of CVEs and hypokalemia in our series are consistent with those of pivotal trials of AA plus PDN, confirming the efficacy and safety of this regimen also in the real-world setting. Elderly patients have higher odds of developing/worsening CVEs. However, regardless of age, CVEs were not associated with worse outcomes. Treatment-related hypokalemia seemed to be associated with longer OS, albeit this finding needs confirmation within larger, prospective series.

https://pubmed.ncbi.nlm.nih.gov/29383035/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Abiraterone acetate and prednisone in the pre- and post-docetaxel setting for metastatic castration-resistant prostate cancer : a mono-institutional experience focused on cardiovascular events and their impact on clinical outcomes . The aim of this work was to to evaluate the incidence and risk factors of adverse events (AEs), focusing on cardiovascular events (CVEs) and hypokalemia, in patients treated with abiraterone acetate (AA) and prednisone (PDN) outside clinical trials, and their association with survival outcomes. ### methods This was a retrospective cohort study of 105 patients treated from 2011 to 2016. Incidence of AEs was descriptively summarized in the whole cohort and by subgroup (pre- ### results Overall, median PFS and OS were 14.9 and 24.6 months, respectively. Prostate-specific antigen (PSA) ⩾ 10 ng/ml ( ### conclusions Median PFS and OS estimates and incidence of CVEs and hypokalemia in our series are consistent with those of pivotal trials of AA plus PDN, confirming the efficacy and safety of this regimen also in the real-world setting. Elderly patients have higher odds of developing/worsening CVEs. However, regardless of age, CVEs were not associated with worse outcomes. Treatment-related hypokalemia seemed to be associated with longer OS, albeit this finding needs confirmation within larger, prospective series. ### Response: Abiraterone, prednisone

9e60e1297fe1d1a7991c6c60ce881374

Nivolumab plus ipilimumab combined therapy is among the most effective therapies for advanced melanoma .

Increased serum CCL26 level is a potential biomarker for the effectiveness of anti-PD1 antibodies in patients with advanced melanoma. Nivolumab plus ipilimumab combined therapy is among the most effective therapies for advanced melanoma . However, this therapy is also associated with a high frequency of immune-related adverse events (irAEs). To avoid such severe irAEs caused by additional administration of anti-CTLA4 antibodies, biomarkers to distinguish responders from non-responders among patients treated with anti-PD1 antibodies are important. The purpose of this study is to evaluate the increased serum levels of CCL11, CCL24, and CCL26 as a predictive biomarker for the efficacy of anti-PD1 antibodies in advanced cutaneous melanoma patients. This study analyzed increased serum levels of CCL11, CCL24, and CCL26 in 46 cases of advanced cutaneous melanoma treated with anti-PD1 antibodies. Serum levels on day 42 were compared to baseline (day 0) and analyzed statistically. Receiver operating characteristic curves were established to evaluate the correlation between serum levels of CCL11, CCL24, and CCL26 and efficacy of anti-PD1 antibodies. Increased serum levels of CCL26 correlated significantly with the efficacy of anti-PD1 antibodies. In contrast, no significant correlations were seen between increased serum levels of CCL11 and CCL24 and efficacy of anti-PD1 antibodies. Increased serum levels of CCL26 may be a useful biomarker for identifying those patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy.

https://pubmed.ncbi.nlm.nih.gov/32658051/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Increased serum CCL26 level is a potential biomarker for the effectiveness of anti-PD1 antibodies in patients with advanced melanoma. Nivolumab plus ipilimumab combined therapy is among the most effective therapies for advanced melanoma . However, this therapy is also associated with a high frequency of immune-related adverse events (irAEs). To avoid such severe irAEs caused by additional administration of anti-CTLA4 antibodies, biomarkers to distinguish responders from non-responders among patients treated with anti-PD1 antibodies are important. The purpose of this study is to evaluate the increased serum levels of CCL11, CCL24, and CCL26 as a predictive biomarker for the efficacy of anti-PD1 antibodies in advanced cutaneous melanoma patients. This study analyzed increased serum levels of CCL11, CCL24, and CCL26 in 46 cases of advanced cutaneous melanoma treated with anti-PD1 antibodies. Serum levels on day 42 were compared to baseline (day 0) and analyzed statistically. Receiver operating characteristic curves were established to evaluate the correlation between serum levels of CCL11, CCL24, and CCL26 and efficacy of anti-PD1 antibodies. Increased serum levels of CCL26 correlated significantly with the efficacy of anti-PD1 antibodies. In contrast, no significant correlations were seen between increased serum levels of CCL11 and CCL24 and efficacy of anti-PD1 antibodies. Increased serum levels of CCL26 may be a useful biomarker for identifying those patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy. ### Response: Nivolumab, ipilimumab

615fe37e6e298fc0bc25eabe90123940

Cells that were sequentially exposed to rapamycin and topotecan had significantly higher levels of cleaved caspase-8 , -3 , and PARP compared to those treated with topotecan alone .

Rapamycin-topotecan combination exhibited enhanced antitumor efficacy compared to topotecan used alone in cisplatin-resistant ovarian cancer cells. The present study aimed to investigate the antitumor efficacy of combination of topotecan with rapamycin, a mTOR inhibitor, in cisplatin-resistant ovarian cancer cells A2780cis and COC1/DDP. Expressions of mTOR and its target molecules p70S6K and 4E-BP1 were determined in A2780cis and COC1/DDP and the parental cells A2780 and COC1 that are sensitive to cisplatin using Western blotting. Cell proliferation was examined using MTT assay in vitro and a nude mouse model in vivo, respectively. Cell apoptosis and the relevant proteins were determined by flow cytometry and Western blotting. We found that the levels of phosphorylated mTOR, p70S6K, and 4E-BP1 were obviously higher in A2780cis and COC1/DDP cells than that in A2780 and COC1 cells. Pretreatment with rapamycin significantly enhanced the effects of topotecan in suppressing cell proliferation and soliciting cell apoptosis in A2780cis and COC1/DDP cells. Cells that were sequentially exposed to rapamycin and topotecan had significantly higher levels of cleaved caspase-8 , -3 , and PARP compared to those treated with topotecan alone . Mice co-administered rapamycin and topotecan had significantly decreased terminal tumor burden without additional loss of bodyweight compared to the mice received topotecan alone. The results suggested that rapamycin sensitized A2780cis and COC1/DDP cells to topotecan-induced apoptosis and rapamycin-topotecan combination might have a value in treatment of cisplatin-resistant ovarian cancer.

https://pubmed.ncbi.nlm.nih.gov/26278147/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Rapamycin-topotecan combination exhibited enhanced antitumor efficacy compared to topotecan used alone in cisplatin-resistant ovarian cancer cells. The present study aimed to investigate the antitumor efficacy of combination of topotecan with rapamycin, a mTOR inhibitor, in cisplatin-resistant ovarian cancer cells A2780cis and COC1/DDP. Expressions of mTOR and its target molecules p70S6K and 4E-BP1 were determined in A2780cis and COC1/DDP and the parental cells A2780 and COC1 that are sensitive to cisplatin using Western blotting. Cell proliferation was examined using MTT assay in vitro and a nude mouse model in vivo, respectively. Cell apoptosis and the relevant proteins were determined by flow cytometry and Western blotting. We found that the levels of phosphorylated mTOR, p70S6K, and 4E-BP1 were obviously higher in A2780cis and COC1/DDP cells than that in A2780 and COC1 cells. Pretreatment with rapamycin significantly enhanced the effects of topotecan in suppressing cell proliferation and soliciting cell apoptosis in A2780cis and COC1/DDP cells. Cells that were sequentially exposed to rapamycin and topotecan had significantly higher levels of cleaved caspase-8 , -3 , and PARP compared to those treated with topotecan alone . Mice co-administered rapamycin and topotecan had significantly decreased terminal tumor burden without additional loss of bodyweight compared to the mice received topotecan alone. The results suggested that rapamycin sensitized A2780cis and COC1/DDP cells to topotecan-induced apoptosis and rapamycin-topotecan combination might have a value in treatment of cisplatin-resistant ovarian cancer. ### Response: rapamycin, topotecan, topotecan

cc4118b0a9d2cafa211a84e7363516a0

No cross-resistance was found with conventional drugs , being PNU-159548 active also in cells resistant to doxorubicin and with a multidrug resistance phenotype ( associated with MDR1 gene/P-glycoprotein overexpression ) , as well as in cells resistant to methotrexate or to cisplatin .

4-Demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyl-daunorubicin (PNU-159548): a promising new candidate for chemotherapeutic treatment of osteosarcoma patients. The effectiveness of the alkycycline 4-demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyl-daunorubicin (PNU-159548, ladirubicin), a new drug with high antitumour activity against a broad range of neoplasms, was evaluated by using a panel of 32 human osteosarcoma cell lines, including cell lines resistant to doxorubicin, methotrexate, or cisplatin. PNU-159548 resulted to be highly active in all cell lines. No cross-resistance was found with conventional drugs , being PNU-159548 active also in cells resistant to doxorubicin and with a multidrug resistance phenotype ( associated with MDR1 gene/P-glycoprotein overexpression ) , as well as in cells resistant to methotrexate or to cisplatin . Analysis of drug-drug interactions showed that PNU-159548 could be successfully used in combination with all the most important drugs currently used in OS chemotherapy. In fact, the simultaneous administration of PNU-159548 and doxorubicin, methotrexate, or cisplatin produced mostly additive or synergistic effects. Sequential exposure to PNU-159548 followed immediately by doxorubicin, methotrexate, or cisplatin was the most effective sequence of administration, invariably resulting in additive or synergistic effects in both drug-sensitive and drug-resistant osteosarcoma cell lines. In conclusion, the high in vitro effectiveness, the absence of cross-resistance with doxorubicin, methotrexate, or cisplatin and the possibility to be successfully used in combination with these drugs indicate PNU-159548 as a promising candidate to be considered for planning new therapeutic regimens for osteosarcoma patients, who show a decreased response to conventional chemotherapy.

https://pubmed.ncbi.nlm.nih.gov/16140527/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: 4-Demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyl-daunorubicin (PNU-159548): a promising new candidate for chemotherapeutic treatment of osteosarcoma patients. The effectiveness of the alkycycline 4-demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyl-daunorubicin (PNU-159548, ladirubicin), a new drug with high antitumour activity against a broad range of neoplasms, was evaluated by using a panel of 32 human osteosarcoma cell lines, including cell lines resistant to doxorubicin, methotrexate, or cisplatin. PNU-159548 resulted to be highly active in all cell lines. No cross-resistance was found with conventional drugs , being PNU-159548 active also in cells resistant to doxorubicin and with a multidrug resistance phenotype ( associated with MDR1 gene/P-glycoprotein overexpression ) , as well as in cells resistant to methotrexate or to cisplatin . Analysis of drug-drug interactions showed that PNU-159548 could be successfully used in combination with all the most important drugs currently used in OS chemotherapy. In fact, the simultaneous administration of PNU-159548 and doxorubicin, methotrexate, or cisplatin produced mostly additive or synergistic effects. Sequential exposure to PNU-159548 followed immediately by doxorubicin, methotrexate, or cisplatin was the most effective sequence of administration, invariably resulting in additive or synergistic effects in both drug-sensitive and drug-resistant osteosarcoma cell lines. In conclusion, the high in vitro effectiveness, the absence of cross-resistance with doxorubicin, methotrexate, or cisplatin and the possibility to be successfully used in combination with these drugs indicate PNU-159548 as a promising candidate to be considered for planning new therapeutic regimens for osteosarcoma patients, who show a decreased response to conventional chemotherapy. ### Response: PNU-159548, doxorubicin, methotrexate, cisplatin

61e5eaac10e21ebad5a2d5e91724cf19

Synergistic cytotoxic effects of recombinant human tumor necrosis factor and Etoposide ( VP16 ) or Doxorubicin on A2774 human epithelial ovarian cancer cell line .

Synergistic cytotoxic effects of recombinant human tumor necrosis factor and Etoposide ( VP16 ) or Doxorubicin on A2774 human epithelial ovarian cancer cell line . Recombinant human tumor necrosis factor (rHuTNF) is a cytokine, with some antitumor activity, released by stimulated monocytes-macrophages. In vivo and in vitro cytotoxicity studies testing the effectiveness of rHuTNF alone or in combination with chemotherapeutic agents have been carried out. We have evaluated the direct cytotoxic effect of rHuTNF on a human epithelial ovarian cancer cell line in vitro (A2774), alone or in combination with etoposide (VP16) or doxorubicin (Doxo), some topoisomerase II (Topo II) targeted drugs, or in combination with cisplatin (CDDP), a not Topo II interactive drug. Our results suggest that rHuTNF is directly cytotoxic and that it is also able to induce a potentiation of VP16- or Doxo-cytotoxicity, but it is unable to potentiate CDDP-cytotoxicity. These data represent a reasonable basis for combining rHuTNF with Topo II inhibitors within phase I studies. The combination regimen could be tested in ovarian cancer patients.

https://pubmed.ncbi.nlm.nih.gov/11576250/

### Instruction: Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds that can co-occur for the mentioned treatment ### Input: Synergistic cytotoxic effects of recombinant human tumor necrosis factor and Etoposide ( VP16 ) or Doxorubicin on A2774 human epithelial ovarian cancer cell line . Recombinant human tumor necrosis factor (rHuTNF) is a cytokine, with some antitumor activity, released by stimulated monocytes-macrophages. In vivo and in vitro cytotoxicity studies testing the effectiveness of rHuTNF alone or in combination with chemotherapeutic agents have been carried out. We have evaluated the direct cytotoxic effect of rHuTNF on a human epithelial ovarian cancer cell line in vitro (A2774), alone or in combination with etoposide (VP16) or doxorubicin (Doxo), some topoisomerase II (Topo II) targeted drugs, or in combination with cisplatin (CDDP), a not Topo II interactive drug. Our results suggest that rHuTNF is directly cytotoxic and that it is also able to induce a potentiation of VP16- or Doxo-cytotoxicity, but it is unable to potentiate CDDP-cytotoxicity. These data represent a reasonable basis for combining rHuTNF with Topo II inhibitors within phase I studies. The combination regimen could be tested in ovarian cancer patients. ### Response: human tumor necrosis factor, Etoposide, Doxorubicin