B1tta/Drug-ACE huggingface dataset:
[Title]: Cetuximab and irinotecan/5-fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma.
[Abstract]: BACKGROUND: To investigate the safety/tolerability of the EGFR-antibody cetuximab when added to irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) for first-line treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Twenty-one patients with untreated, metastatic, EGFR-expressing CRC received cetuximab 400 mg/m(2) as an initial dose, and thereafter 250 mg/m(2) weekly. In addition, patients received infusional 5-FU (24 h) in two dose levels (1500 mg/m(2), low 5-FU group, n = 6 or 2000 mg/m(2), high 5-FU group, n = 15), plus FA at 500 mg/m(2) and irinotecan at 80 mg/m(2), weekly x6 q50d. RESULTS: Twenty patients were assessable for tolerability after the first cycle. There were no dose limiting toxicities (DLTs) in the low 5-FU group and three DLTs (20%) in the high 5-FU group (two patients with diarrhea grade 3 and one patient with diarrhea grade 4). In the low 5-FU group all six patients received &gt;80% of the planned dose. In the high 5-FU group, seven of 14 patients (50%) received &lt; or =80% of the planned chemotherapy dose during the first cycle due to dosage reductions whilst treatment delays occurred in 10/14 patients. During the whole study period, the common grade 3/4 adverse events were acne-like rash (38%) and diarrhea (29%). Chemotherapy did not affect the pharmacokinetics of cetuximab determined at weeks 1 and 4. Fourteen patients (67%, 95% CI 47% to 87%) had a confirmed response, and six (29%) had stable disease. Median time to progression was 9.9 months [lower 95% confidence limit (CL) 7.9, upper 95% CL not reached]. Median survival time was 33 months (lower CL 20, upper CL not reached). Four patients received secondary surgery with curative intent, and a fifth was potentially eligible for surgery but declined. CONCLUSIONS: Addition of cetuximab to weekly infusional 5-FU/FA plus irinotecan is safe and first data suggest a promising activity. The 5-FU dose of 1500 mg/m(2) is recommended for further studies.
[Drug-Disease]: 5-fluorouracil - colorectal cancer
[Title]: Combination therapy with thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma not undergoing upfront autologous stem cell transplantation: a phase II trial.
[Abstract]: BACKGROUND AND OBJECTIVES: Thalidomide plus dexamethasone (Thal/Dex) has emerged as an effective alternative to vincristine, doxorubicin and dexamethasone as a pre-transplant induction therapy for newly diagnosed multiple myeloma. However, many patients treated initially with Thal/Dex do not proceed to autologous stem cell transplantation (ASCT) and the time to progression and other outcome measures with Thal/Dex as primary therapy for multiple myeloma are not known. We present the first data on the outcome of patients with newly diagnosed multiple myeloma treated with Thal/Dex who did not undergo upfront ASCT. DESIGN AND METHODS: We identified 21 patients with newly diagnosed multiple myeloma treated with Thal/Dex on a phase II clinical trial who did not undergo ASCT due to age, comorbidity or the patient's refusal. Patients received thalidomide at a dose of 200 mg/day orally and dexamethasone 40 mg daily on days 1-4, 9-12, 17-20 (odd months) and days 1-4 (even months). Cycles were repeated every 28 days. RESULTS: The median age was 66 years (range 36-78). The median duration of follow-up was 21 months (range 1-52). One (5%) patient achieved a complete response, and 9 (43%) had a partial response, so the overall response rate was 48%. Of the remaining patients, 7 (33.3%) had stable disease, one patient did not respond, and three died while on therapy prior to response assessment. The median overall survival and time to progression were 21 months and 18 months, respectively. INTERPRETATION AND CONCLUSIONS: The median time to disease progression in patients with multiple myeloma who receive initial therapy with Thal/Dex and who do not undergo ASCT is 18 months.
[Drug-Disease]: dexamethasone - multiple myeloma
[Title]: Combination therapy with thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma not undergoing upfront autologous stem cell transplantation: a phase II trial.
[Abstract]: BACKGROUND AND OBJECTIVES: Thalidomide plus dexamethasone (Thal/Dex) has emerged as an effective alternative to vincristine, doxorubicin and dexamethasone as a pre-transplant induction therapy for newly diagnosed multiple myeloma. However, many patients treated initially with Thal/Dex do not proceed to autologous stem cell transplantation (ASCT) and the time to progression and other outcome measures with Thal/Dex as primary therapy for multiple myeloma are not known. We present the first data on the outcome of patients with newly diagnosed multiple myeloma treated with Thal/Dex who did not undergo upfront ASCT. DESIGN AND METHODS: We identified 21 patients with newly diagnosed multiple myeloma treated with Thal/Dex on a phase II clinical trial who did not undergo ASCT due to age, comorbidity or the patient's refusal. Patients received thalidomide at a dose of 200 mg/day orally and dexamethasone 40 mg daily on days 1-4, 9-12, 17-20 (odd months) and days 1-4 (even months). Cycles were repeated every 28 days. RESULTS: The median age was 66 years (range 36-78). The median duration of follow-up was 21 months (range 1-52). One (5%) patient achieved a complete response, and 9 (43%) had a partial response, so the overall response rate was 48%. Of the remaining patients, 7 (33.3%) had stable disease, one patient did not respond, and three died while on therapy prior to response assessment. The median overall survival and time to progression were 21 months and 18 months, respectively. INTERPRETATION AND CONCLUSIONS: The median time to disease progression in patients with multiple myeloma who receive initial therapy with Thal/Dex and who do not undergo ASCT is 18 months.
[Drug-Disease]: Thal - multiple myeloma
[Title]: Study on the efficacy and safety of adefovir dipivoxil treatment in post-liver transplant patients with hepatitis B virus infection and lamivudine-resistant hepatitis B virus.
[Abstract]: Hepatitis B virus (HBV) recurrence and de novo HBV infection are frequent events in liver transplantation recipients. Treatment with lamivudine is initially efficient in both infections but the incidence of lamivudine-resistant HBV emergence increases over time. Adefovir appears to be promising in post-liver transplantation patients with recurrent HBV infection and lamivudine-resistant HBV. This study analyzed adefovir treatment in 42 post-liver transplantation patients who developed recurrent HBV or de novo HBV infection with lamivudine-resistant HBV (54.8% HCV-coinfected). Patients received 10 mg of oral adefovir once daily for a mean period of time of 21.5 months (range from 12 to 31 months). In 62.9% of patients, ALT levels decreased significantly. Serum HBV-DNA was undetectable in 64% of the cases. Twenty percent of patients lost HBeAg marker and 13.3% of them developed anti-HBe. In 9.5% of recipients, HBsAg became negative. There was no significant change in serum creatinine levels. In only one patient was worsening of the renal function detected, making dose adjustment necessary. No other side effects were reported. Our results confirm the efficacy and safety of adefovir treatment in post-liver transplantation patients with lamivudine-resistant HBV, neither were adefovir-resistant mutations identified in patients after 21 months of therapy, nor were there adverse events, especially renal toxicity.
[Drug-Disease]: adefovir dipivoxil - HBV infection
[Title]: Thiopurine S-methyltransferase polymorphisms and the relationship between the mutant alleles and the adverse effects in systemic lupus erythematosus patients taking azathioprine.
[Abstract]: OBJECTIVE: The present study sought to elucidate the genetic basis of thiopurine methyltransferase (TPMT) polymorphism and subsequently to investigate the relationship between mutant TPMT and an adverse response observed in Korean patients with systemic lupus erythematosus (SLE) taking azathioprine (AZA). METHODS: The TPMT genotype of 342 patients with SLE was determined by MALDI-TOF mass spectrometry and correlated with the effects of clinical exposure to AZA. RESULTS: TPMT polymorphism was detected in 17 of the 342 study subjects (5.0%), 12 heterozygous for the TPMT*3C allele and 5 heterozygous for the TPMT*6 allele. Numerous patients taking AZA demonstrated adverse drug responses. Severe nausea occurred in 4 patients with the TPMT*3C allele, while 1 patient with the TPMT*6 allele suffered severe bone marrow toxicity. Leucopenia (n = 17), nausea (n = 4), and abnormal liver function (n = 1) were suspected in 23 of the 94 lupus patients taking AZA. AZA was relatively well tolerated by the remainder of the patients. The heterozygous genotype for the TPMT*3C and *6 alleles was frequently detected in Korean SLE patients. CONCLUSION: Contrary to previous hypotheses, this study identified no statistical correlation between TPMT genotype and AZA toxicity. We thus conclude that TMPT genotyping cannot replace regular blood monitoring in SLE patients receiving AZA treatment.
[Drug-Disease]: AZA - SLE
[Title]: The efficacy of olanzapine for decreasing cue-elicited craving in individuals with schizophrenia and cocaine dependence: a preliminary report.
[Abstract]: OBJECTIVE: Although a growing body of research suggests that atypical neuroleptic medications are efficacious in the treatment of cocaine addiction among individuals with schizophrenia, more rigorously controlled trials are needed. To extend this research, we performed a 6-week double-blind study comparing olanzapine to haloperidol with the primary objective of reducing cue-elicited cocaine craving and the secondary aims of decreasing substance use, improving psychiatric symptoms, and determining an effect size for future studies. METHODS: Thirty-one subjects with cocaine dependence and schizophrenia were randomized to olanzapine or haloperidol, underwent a cue-exposure procedure, and completed psychiatric and substance abuse ratings. RESULTS: Individuals in the olanzapine group who completed the study had a significant reduction on the energy subscale of the Voris Cocaine Craving Scale at study completion compared with individuals in the haloperidol group. The olanzapine-treated group also had lower, but not statistically significant, PANSS General Psychopathology Subscale scores and fewer positive urine toxicology screens compared with those in the haloperidol group. CONCLUSION: This small, but rigorously controlled, pilot trial provides additional evidence for the use of atypical antipsychotics for the treatment of individuals with co-occurring schizophrenia and cocaine dependence. Reductions in craving were associated with medium to large effect sizes.
[Drug-Disease]: olanzapine - cocaine addiction
[Title]: Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease.
[Abstract]: Mild-to-moderate AD patients were randomized to placebo or rosiglitazone (RSG) 2, 4 or 8 mg. Primary end points at Week 24 were mean change from baseline in AD Assessment Scale-Cognitive (ADAS-Cog) and Clinician's Interview-Based Impression of Change Plus Caregiver Input global scores in the intention-to-treat population (N=511), and results were also stratified by apolipoprotein E (APOE) genotype (n=323). No statistically significant differences on primary end points were detected between placebo and any RSG dose. There was a significant interaction between APOE epsilon4 allele status and ADAS-Cog (P=0.014). Exploratory analyses demonstrated significant improvement in ADAS-Cog in APOE epsilon4-negative patients on 8 mg RSG (P=0.024; not corrected for multiplicity). APOE epsilon4-positive patients did not show improvement and showed a decline at the lowest RSG dose (P=0.012; not corrected for multiplicity). Exploratory analyses suggested that APOE epsilon4 non-carriers exhibited cognitive and functional improvement in response to RSG, whereas APOE epsilon4 allele carriers showed no improvement and some decline was noted. These preliminary findings require confirmation in appropriate clinical studies.
[Drug-Disease]: RSG - AD
[Title]: Six-month trial of bupropion with contingency management for cocaine dependence in a methadone-maintained population.
[Abstract]: CONTEXT: No effective pharmacotherapies exist for cocaine dependence, although contingency management (CM) has demonstrated efficacy. OBJECTIVE: To compare the efficacy of bupropion hydrochloride and CM for reducing cocaine use in methadone hydrochloride-maintained individuals. DESIGN: This 25-week, placebo-controlled, double-blind trial randomly assigned participants to 1 of 4 treatment conditions: CM and placebo (CMP), CM and 300 mg/d of bupropion hydrochloride (CMB), voucher control and placebo (VCP), or voucher control and bupropion (VCB). SETTING: Outpatient clinic at the Veterans Affairs Connecticut Healthcare System. PARTICIPANTS: A total of 106 opiate-dependent, cocaine-abusing individuals. INTERVENTIONS: All study participants received methadone hydrochloride (range, 60-120 mg). Participants receiving bupropion hydrochloride were given 300 mg/d beginning at week 3. In the CM conditions, each urine sample negative for both opioids and cocaine resulted in a monetary-based voucher that increased for consecutively drug-free urine samples during weeks 1 to 13. Completion of abstinence-related activities also resulted in a voucher. During weeks 14 to 25, only completion of activities was reinforced in the CM group, regardless of sample results. The voucher control groups received vouchers for submitting urine samples, regardless of results, throughout the study. MAIN OUTCOME MEASURE: Thrice-weekly urine toxicologic test results for cocaine and heroin. RESULTS: Groups did not differ in baseline characteristics or retention rates. Opiate use decreased significantly, with all treatment groups attaining equivalent amounts of opiate use at the end of the study. In the CMB group, the proportion of cocaine-positive samples significantly decreased during weeks 3 to 13 (P&lt;.001) relative to week 3 and remained low during weeks 14 to 25. In the CMP group, cocaine use significantly increased during weeks 3 to 13 (P&lt;.001) relative to week 3, but then cocaine use significantly decreased relative to the initial slope during weeks 14 to 25 (P&lt;.001). In contrast, by treatment end, the VCB and VCP groups showed no significant improvement in cocaine use. CONCLUSION: These findings suggest that combining CM with bupropion for the treatment of cocaine addiction may significantly improve outcomes relative to bupropion alone.
[Drug-Disease]: bupropion - cocaine addiction
[Title]: MEK1 inhibition sensitizes primary acute myelogenous leukemia to arsenic trioxide-induced apoptosis.
[Abstract]: We found that MEK1 inhibitor PD184352 strikingly increased apoptosis induced by arsenic trioxide (ATO) in 21 of 25 patients with primary acute myelogenous leukemia (AML). Isobologram analysis confirmed the synergistic (13 of 25 patients) or additive (8 of 25 patients) nature of this interaction. Moreover, we demonstrated that the p53-related gene p73 is a molecular target of the combined treatment in AML blasts. Indeed, ATO modulates the expression of the p73 gene by inducing the proapoptotic and antiproliferative TAp73 and the antiapoptotic and proproliferative DeltaNp73 isoforms, thereby failing to elevate the TA/DeltaNp73 ratio. Conversely, treatment with PD184352 reduces the level of DeltaNp73 and blunts the arsenic-mediated up-regulation of DeltaNp73, thus causing an increase in the TA/DeltaNp73 ratio of dual-treated cells. High doses of ATO induced p53 accumulation in 11 of 21 patients. Combined treatment resulted in the induction of the proapoptotic p53/p73 target gene p53AIP1 (p53-regulated apoptosis-inducing protein 1) and greatly enhanced the apoptosis of treated cells.
[Drug-Disease]: PD184352 - AML
[Title]: MEK1 inhibition sensitizes primary acute myelogenous leukemia to arsenic trioxide-induced apoptosis.
[Abstract]: We found that MEK1 inhibitor PD184352 strikingly increased apoptosis induced by arsenic trioxide (ATO) in 21 of 25 patients with primary acute myelogenous leukemia (AML). Isobologram analysis confirmed the synergistic (13 of 25 patients) or additive (8 of 25 patients) nature of this interaction. Moreover, we demonstrated that the p53-related gene p73 is a molecular target of the combined treatment in AML blasts. Indeed, ATO modulates the expression of the p73 gene by inducing the proapoptotic and antiproliferative TAp73 and the antiapoptotic and proproliferative DeltaNp73 isoforms, thereby failing to elevate the TA/DeltaNp73 ratio. Conversely, treatment with PD184352 reduces the level of DeltaNp73 and blunts the arsenic-mediated up-regulation of DeltaNp73, thus causing an increase in the TA/DeltaNp73 ratio of dual-treated cells. High doses of ATO induced p53 accumulation in 11 of 21 patients. Combined treatment resulted in the induction of the proapoptotic p53/p73 target gene p53AIP1 (p53-regulated apoptosis-inducing protein 1) and greatly enhanced the apoptosis of treated cells.
[Drug-Disease]: ATO - AML
[Title]: Lamotrigine for bipolar disorder and comorbid cocaine dependence: a replication and extension study.
[Abstract]: BACKGROUND: Bipolar disorder (BPD) is associated with high rates of substance abuse. We previously reported favorable results with lamotrigine in 30 patients with BPD and cocaine dependence. This report examines lamotrigine therapy in an additional 32 cocaine dependent patients. Data on these 32 participants are presented as a replication study. In addition, we extend the previous findings by combining data from both groups, and by exploring predictors of response. METHOD: Participants received a baseline evaluation and assessment for up to 36weeks with the 17-item Hamilton Rating Scale for Depression (HRSD(17)), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS(18)), and Cocaine Craving Questionnaire (CCQ). Urine samples were obtained, and participants reported drug use during the previous week. RESULTS: In the replication sample (n=32), significant improvements were observed in HRSD(17), YMRS, BPRS(18), and CCQ (baseline to exit), as well as on dollars/week spent on cocaine. In the extension study, the original sample (n=30) and the replication sample (n=32) were combined for a total of 62 participants in the intent-to-treat sample. HRSD(17), YMRS, BPRS(18), and CCQ scores, as well as dollars spent on cocaine, decreased significantly. LIMITATIONS: The study has an open-label, uncontrolled design. CONCLUSION: Lamotrigine treatment was associated with significant improvements in mood, drug craving, and drug use. Controlled trials are needed.
[Drug-Disease]: Lamotrigine - Bipolar disorder
[Title]: Lamotrigine for bipolar disorder and comorbid cocaine dependence: a replication and extension study.
[Abstract]: BACKGROUND: Bipolar disorder (BPD) is associated with high rates of substance abuse. We previously reported favorable results with lamotrigine in 30 patients with BPD and cocaine dependence. This report examines lamotrigine therapy in an additional 32 cocaine dependent patients. Data on these 32 participants are presented as a replication study. In addition, we extend the previous findings by combining data from both groups, and by exploring predictors of response. METHOD: Participants received a baseline evaluation and assessment for up to 36weeks with the 17-item Hamilton Rating Scale for Depression (HRSD(17)), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS(18)), and Cocaine Craving Questionnaire (CCQ). Urine samples were obtained, and participants reported drug use during the previous week. RESULTS: In the replication sample (n=32), significant improvements were observed in HRSD(17), YMRS, BPRS(18), and CCQ (baseline to exit), as well as on dollars/week spent on cocaine. In the extension study, the original sample (n=30) and the replication sample (n=32) were combined for a total of 62 participants in the intent-to-treat sample. HRSD(17), YMRS, BPRS(18), and CCQ scores, as well as dollars spent on cocaine, decreased significantly. LIMITATIONS: The study has an open-label, uncontrolled design. CONCLUSION: Lamotrigine treatment was associated with significant improvements in mood, drug craving, and drug use. Controlled trials are needed.
[Drug-Disease]: Lamotrigine - cocaine dependence
[Title]: Phase I study of S-1 and biweekly docetaxel combination chemotherapy for advanced and recurrent gastric cancer.
[Abstract]: A phase I study of S-1 and biweekly docetaxel (DOC) combination therapy was conducted to determine the maximum tolerated dose (MTD) and pharmacokinetic parameters. Fourteen patients with advanced or recurrent gastric cancer were analyzed. The treatment consisted of S-1 [body surface area (BSA) &lt;1.25 m2:80 mg/day, 1.25&lt;or= BSA &lt;1.50 m2: 100 mg/day, 1.50 m2&lt;or= BSA; 120 mg/day, orally, day 1-14) and DOC (30-40 mg/m2/day, intravenously, day 1 and 15], which were repeated as often as possible every four weeks. Pharmacokinetic analysis was done at DOC 40 mg/m2/day. Initially, patients were administered S-1 and 40 mg/m2/day of DOC, and DOC 40 mg/m2/day was considered as MTD. In detail, one patient developed neutropenia (grade 4, G4), and two other patients had no day 15 DOC administration because of neutropenia (grade 3, G3). When S-1 and 35 mg/m2/day of DOC were administered to three patients, no adverse reactions were noted. In six patients treated with S-1 and 30 mg/m2/day of DOC, one patient developed neutropenia (G4), and another patient developed diarrhea (G3) and anorexia (G3). The rest of this cohort showed no adverse reactions. Although 5-fluorouracil and gimeracil concentrations remained high under impaired renal function, no pharmacokinetic interactions appeared between S-1 and DOC under normal renal function. The dose limiting toxicity of a combination of S-1 and biweekly DOC was leukopenia and neutropenia. The recommended dose for this combination in phase II study is DOC 35 mg/m2/day.
[Drug-Disease]: DOC - anorexia
[Title]: Phase I study of S-1 and biweekly docetaxel combination chemotherapy for advanced and recurrent gastric cancer.
[Abstract]: A phase I study of S-1 and biweekly docetaxel (DOC) combination therapy was conducted to determine the maximum tolerated dose (MTD) and pharmacokinetic parameters. Fourteen patients with advanced or recurrent gastric cancer were analyzed. The treatment consisted of S-1 [body surface area (BSA) &lt;1.25 m2:80 mg/day, 1.25&lt;or= BSA &lt;1.50 m2: 100 mg/day, 1.50 m2&lt;or= BSA; 120 mg/day, orally, day 1-14) and DOC (30-40 mg/m2/day, intravenously, day 1 and 15], which were repeated as often as possible every four weeks. Pharmacokinetic analysis was done at DOC 40 mg/m2/day. Initially, patients were administered S-1 and 40 mg/m2/day of DOC, and DOC 40 mg/m2/day was considered as MTD. In detail, one patient developed neutropenia (grade 4, G4), and two other patients had no day 15 DOC administration because of neutropenia (grade 3, G3). When S-1 and 35 mg/m2/day of DOC were administered to three patients, no adverse reactions were noted. In six patients treated with S-1 and 30 mg/m2/day of DOC, one patient developed neutropenia (G4), and another patient developed diarrhea (G3) and anorexia (G3). The rest of this cohort showed no adverse reactions. Although 5-fluorouracil and gimeracil concentrations remained high under impaired renal function, no pharmacokinetic interactions appeared between S-1 and DOC under normal renal function. The dose limiting toxicity of a combination of S-1 and biweekly DOC was leukopenia and neutropenia. The recommended dose for this combination in phase II study is DOC 35 mg/m2/day.
[Drug-Disease]: DOC - diarrhea