B1tta/Drug-ACE huggingface dataset:
[Title]: Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group.
[Abstract]: BACKGROUND: In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m(2) intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m(2) i.v. on Days 2-5, and interferon alpha (IFNalpha) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m(2) i.v. for 2 days can be combined safely with DTIC, FM, and IFNalpha. Herein, the authors report the results of a Phase II trial with this regimen. METHODS: From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m(2) i.v. on Day 1, DTIC 300 mg/m(2) i.v. on Days 2-4, and CDDP 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks. IFN alpha2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression. RESULTS: A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN alpha2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy. CONCLUSIONS: The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed.
[Drug-Disease]: FM - melanoma
[Title]: Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group.
[Abstract]: BACKGROUND: In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m(2) intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m(2) i.v. on Days 2-5, and interferon alpha (IFNalpha) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m(2) i.v. for 2 days can be combined safely with DTIC, FM, and IFNalpha. Herein, the authors report the results of a Phase II trial with this regimen. METHODS: From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m(2) i.v. on Day 1, DTIC 300 mg/m(2) i.v. on Days 2-4, and CDDP 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks. IFN alpha2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression. RESULTS: A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN alpha2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy. CONCLUSIONS: The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed.
[Drug-Disease]: CDDP - melanoma
[Title]: Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group.
[Abstract]: BACKGROUND: In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m(2) intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m(2) i.v. on Days 2-5, and interferon alpha (IFNalpha) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m(2) i.v. for 2 days can be combined safely with DTIC, FM, and IFNalpha. Herein, the authors report the results of a Phase II trial with this regimen. METHODS: From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m(2) i.v. on Day 1, DTIC 300 mg/m(2) i.v. on Days 2-4, and CDDP 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks. IFN alpha2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression. RESULTS: A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN alpha2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy. CONCLUSIONS: The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed.
[Drug-Disease]: DTIC - melanoma
[Title]: Pharmacodynamics of orally administered sustained- release hydromorphone in humans.
[Abstract]: BACKGROUND: The disposition kinetics of hydromorphone generally necessitates oral administration every 4 h of the conventional immediate-release tablet to provide sustained pain relief. This trial examined time course and magnitude of analgesia to experimental pain after administration of sustained-release hydromorphone as compared with that after immediate-release hydromorphone or placebo. METHODS: Using a 4 x 4 Latin square double-blind design, 12 subjects were randomized to receive a single dose of 8, 16, and 32 mg sustained-release hydromorphone and placebo. The same subjects had received 8 mg immediate-release hydromorphone before this study. Using an electrical experimental pain paradigm, analgesic effects were assessed for up to 30 h after administration, and venous hydromorphone plasma concentrations were measured at corresponding times. RESULTS: The hydromorphone plasma concentration peaked significantly later (12.0 h [12.0--18.0] vs. 0.8 h [0.8--1.0]; median and interquartile range) but was maintained significantly longer at greater than 50% of peak concentration (22.7 +/- 8.2 h vs. 1.1 +/- 0.7 h; mean +/- SD) after sustained-release than after immediate-release hydromorphone. Similarly, sustained-release hydromorphone produced analgesic effects that peaked significantly later (9.0 h [9.0--12.0] vs. 1.5 h [1.0--2.0]) but were maintained significantly longer at greater than 50% of peak analgesic effect (13.3 +/- 6.3 h vs. 3.6 +/- 1.7 h). A statistically significant linear relation between the hydromorphone plasma concentration and the analgesic effect on painful stimuli existed. CONCLUSION: A single oral dose of a new sustained-release formulation of hydromorphone provided analgesia to experimental pain beyond 24 h of its administration.
[Drug-Disease]: hydromorphone - pain
[Title]: [Quality of life of migraine patients after treatment with 2.5 mg oral naratriptan].
[Abstract]: OBJECTIVES: The primary objective of this prospective, open, non controlled, multicenter study was to collect data on migraine patient's health related quality of life before and after treatment of their migraine attacks b naratriptan orl 2.5 mg over a 12 week period. METHODS: The impact on health related quality of life was evaluated by the mean change from pre-treatment scores on the French migraine health related quality of life specific questionnaire (QVM). RESULTS: 244 patients have been included in the study. A statistically significant score improvement in health related quality of life, as measured by the global score and the four scores related to the four dimensions of the QVM questionnaire (functional, psychological, social and therapeutic) was observed compared to the pre-treatment score values. At the end of the treatment period, 67% of patients preferred naratriptan oral 2.5 mg to their usual treatment. CONCLUSION: Those data suggest that the use of naratriptan oral 2.5 mg for the treatment of migraine attacks during a 12 week period may be associated with a significant improvement in migraine patient's quality of life.
[Drug-Disease]: naratriptan - migraine
[Title]: Glomerular and tubular renal functions after long-term medication of sulphasalazine, olsalazine, and mesalazine in patients with ulcerative colitis.
[Abstract]: To date there are only few reports evaluating the potential nephrotoxic reactions of the new 5-aminosalicylic acid (5-ASA) preparations in patients with ulcerative colitis (UC). The aim of this study was to screen the tubular and glomerular functions in patients with UC in maintenance treatment with either 5-ASA azo-compounds (sulphasalazine and olsalazine) or mesalazine. Patients with UC in clinical remission treated with either sulphasalazine, olsalazine, or mesalazine for more than 1 year were included in an open, single-blind retrospective Norwegian multicenter study. Serum and urine creatinine, serum and urine beta2-microglobulin, urine N-acetyl-beta-glucoseamidase (NAG), urine alkaline phosphatase, urine microalbumin, urine alanine amino peptidase, and urine beta2-microglobulin were measured. Fifty-two females and 75 males (n = 127), ages 20-69, were evaluated. Thirty-six patients were treated with sulphasalazine (mean treatment time 10.1+/-6.6 years [mean +/- SD]), 32 patients were treated with olsalazine (2.3+/-1.4 years), and 59 patients with mesalazine (3.2+/-2.0 years). At inclusion, there were no significant differences in the serum or urine values between the groups. In 17 patients (1 patient [3%] in the sulphasalazine group, 4 patients [13%] in the olsalazine group, and 12 patients [20%] in the mesalazine group), at least one abnormal serum and/or urine value was detected. After 10 years of treatment, only one abnormal value was found among the 19 patients in the sulphasalazine group. The abnormal values observed in the other groups indicated minor glomerular or tubular renal damage. In conclusion, long term sulphasalazine treatment appears to be safe and free of nephrotoxic side effects, whereas minor glomerular and tubular impairment are observed in a few patients treated with olsalazine and mesalazine.
[Drug-Disease]: olsalazine - ulcerative colitis
[Title]: Glomerular and tubular renal functions after long-term medication of sulphasalazine, olsalazine, and mesalazine in patients with ulcerative colitis.
[Abstract]: To date there are only few reports evaluating the potential nephrotoxic reactions of the new 5-aminosalicylic acid (5-ASA) preparations in patients with ulcerative colitis (UC). The aim of this study was to screen the tubular and glomerular functions in patients with UC in maintenance treatment with either 5-ASA azo-compounds (sulphasalazine and olsalazine) or mesalazine. Patients with UC in clinical remission treated with either sulphasalazine, olsalazine, or mesalazine for more than 1 year were included in an open, single-blind retrospective Norwegian multicenter study. Serum and urine creatinine, serum and urine beta2-microglobulin, urine N-acetyl-beta-glucoseamidase (NAG), urine alkaline phosphatase, urine microalbumin, urine alanine amino peptidase, and urine beta2-microglobulin were measured. Fifty-two females and 75 males (n = 127), ages 20-69, were evaluated. Thirty-six patients were treated with sulphasalazine (mean treatment time 10.1+/-6.6 years [mean +/- SD]), 32 patients were treated with olsalazine (2.3+/-1.4 years), and 59 patients with mesalazine (3.2+/-2.0 years). At inclusion, there were no significant differences in the serum or urine values between the groups. In 17 patients (1 patient [3%] in the sulphasalazine group, 4 patients [13%] in the olsalazine group, and 12 patients [20%] in the mesalazine group), at least one abnormal serum and/or urine value was detected. After 10 years of treatment, only one abnormal value was found among the 19 patients in the sulphasalazine group. The abnormal values observed in the other groups indicated minor glomerular or tubular renal damage. In conclusion, long term sulphasalazine treatment appears to be safe and free of nephrotoxic side effects, whereas minor glomerular and tubular impairment are observed in a few patients treated with olsalazine and mesalazine.
[Drug-Disease]: sulphasalazine - ulcerative colitis
[Title]: Glomerular and tubular renal functions after long-term medication of sulphasalazine, olsalazine, and mesalazine in patients with ulcerative colitis.
[Abstract]: To date there are only few reports evaluating the potential nephrotoxic reactions of the new 5-aminosalicylic acid (5-ASA) preparations in patients with ulcerative colitis (UC). The aim of this study was to screen the tubular and glomerular functions in patients with UC in maintenance treatment with either 5-ASA azo-compounds (sulphasalazine and olsalazine) or mesalazine. Patients with UC in clinical remission treated with either sulphasalazine, olsalazine, or mesalazine for more than 1 year were included in an open, single-blind retrospective Norwegian multicenter study. Serum and urine creatinine, serum and urine beta2-microglobulin, urine N-acetyl-beta-glucoseamidase (NAG), urine alkaline phosphatase, urine microalbumin, urine alanine amino peptidase, and urine beta2-microglobulin were measured. Fifty-two females and 75 males (n = 127), ages 20-69, were evaluated. Thirty-six patients were treated with sulphasalazine (mean treatment time 10.1+/-6.6 years [mean +/- SD]), 32 patients were treated with olsalazine (2.3+/-1.4 years), and 59 patients with mesalazine (3.2+/-2.0 years). At inclusion, there were no significant differences in the serum or urine values between the groups. In 17 patients (1 patient [3%] in the sulphasalazine group, 4 patients [13%] in the olsalazine group, and 12 patients [20%] in the mesalazine group), at least one abnormal serum and/or urine value was detected. After 10 years of treatment, only one abnormal value was found among the 19 patients in the sulphasalazine group. The abnormal values observed in the other groups indicated minor glomerular or tubular renal damage. In conclusion, long term sulphasalazine treatment appears to be safe and free of nephrotoxic side effects, whereas minor glomerular and tubular impairment are observed in a few patients treated with olsalazine and mesalazine.
[Drug-Disease]: mesalazine - ulcerative colitis
[Title]: Use of amifostine as a chemoprotectant during high-dose chemotherapy in autologous peripheral blood stem cell transplantation.
[Abstract]: This report describes two patients with germ cell tumors who underwent tandem autologous peripheral stem cell transplants. The chemotherapy consisted of high-dose carboplatin and etoposide. Both patients developed chemotherapy-related toxicities, which included nephrotoxicity in one case and febrile neutropenia, thrombocytopenia, ototoxicity and mucositis in both. During the second transplant, both patients received amifostine 15 min before and 2 h after each dose of carboplatin. The patients had less mucositis and nephrotoxicity. The duration of neutropenia and thrombocytopenia was less in both cases resulting in a decreased use of antibiotics and platelet transfusions. These cases suggest that the use of amifostine may be of benefit in minimizing toxicities associated with high-dose chemotherapy.
[Drug-Disease]: amifostine - nephrotoxicity
[Title]: Use of amifostine as a chemoprotectant during high-dose chemotherapy in autologous peripheral blood stem cell transplantation.
[Abstract]: This report describes two patients with germ cell tumors who underwent tandem autologous peripheral stem cell transplants. The chemotherapy consisted of high-dose carboplatin and etoposide. Both patients developed chemotherapy-related toxicities, which included nephrotoxicity in one case and febrile neutropenia, thrombocytopenia, ototoxicity and mucositis in both. During the second transplant, both patients received amifostine 15 min before and 2 h after each dose of carboplatin. The patients had less mucositis and nephrotoxicity. The duration of neutropenia and thrombocytopenia was less in both cases resulting in a decreased use of antibiotics and platelet transfusions. These cases suggest that the use of amifostine may be of benefit in minimizing toxicities associated with high-dose chemotherapy.
[Drug-Disease]: amifostine - mucositis
[Title]: Adverse effects of early dexamethasone treatment in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network.
[Abstract]: BACKGROUND: Early administration of high doses of dexamethasone may reduce the risk of chronic lung disease in premature infants but can cause complications. Whether moderate doses would be as effective but safer is not known. METHODS: We randomly assigned 220 infants with a birth weight of 501 to 1000 g who were treated with mechanical ventilation within 12 hours after birth to receive dexamethasone or placebo with either routine ventilatory support or permissive hypercapnia. The dexamethasone was administered within 24 hours after birth at a dose of 0.15 mg per kilogram of body weight per day for three days, followed by a tapering of the dose over a period of seven days. The primary outcome was death or chronic lung disease at 36 weeks' postmenstrual age. RESULTS: The relative risk of death or chronic lung disease in the dexamethasone-treated infants, as compared with those who received placebo, was 0.9 (95 percent confidence interval, 0.8 to 1.1). Since the effect of dexamethasone treatment did not vary according to the ventilatory approach, the two dexamethasone groups and the two placebo groups were combined. The infants in the dexamethasone group were less likely than those in the placebo group to be receiving oxygen supplementation 28 days after birth (P=0.004) or open-label dexamethasone (P=0.01), were more likely to have hypertension (P<0.001), and were more likely to be receiving insulin treatment for hyperglycemia (P=0.02). During the first 14 days, spontaneous gastrointestinal perforation occurred in a larger proportion of infants in the dexamethasone group (13 percent, vs. 4 percent in the placebo group; P=0.02). The dexamethasone-treated infants had a lower weight (P=0.02) and a smaller head circumference (P=0.04) at 36 weeks' postmenstrual age. CONCLUSIONS: In preterm infants, early administration of dexamethasone at a moderate dose has no effect on death or chronic lung disease and is associated with gastrointestinal perforation and decreased growth.
[Drug-Disease]: dexamethasone - lung disease
[Title]: Ciprofloxacin increases serum clozapine and N-desmethylclozapine: a study in patients with schizophrenia.
[Abstract]: OBJECTIVE: A possible pharmacokinetic interaction between a CYP1A2 inhibitor, ciprofloxacin, and clozapine was studied in schizophrenia patients with stable clozapine treatment. METHODS: A randomised double-blind cross-over study design with two phases was used. Seven schizophrenic inpatients volunteered to receive, in addition to their previous drug regimen, either 250 mg ciprofloxacin or placebo twice daily (b.i.d.) for 7 days. The phases were separated by a 7-day wash-out period. Serum concentrations of clozapine and its main metabolite N-desmethylclozapine were measured during both phases before the first dose on day 1 and on days 3 and 8. RESULTS: Ciprofloxacin increased mean serum concentration of clozapine and N-desmethylclozapine by 29% (P < 0.01) and 31% (P < 0.05), respectively. There was a significant positive correlation (r = 0.90, P < 0.01) between the individual concentrations of serum ciprofloxacin and the increase in concentrations of clozapine plus N-desmethylclozapine. The increase in serum clozapine concentrations correlated significantly (r = 0.89, P < 0.01) with the ratios of N-desmethylclozapine to clozapine concentrations. CONCLUSION: Even a low dose of ciprofloxacin can moderately increase serum concentrations of clozapine and N-desmethylclozapine. A probable mechanism of interaction is an inhibition of CYP1A2 enzyme by ciprofloxacin. The possibility of clinically significant interaction should be considered, especially when higher doses of ciprofloxacin are used concomitantly with clozapine.
[Drug-Disease]: N-desmethylclozapine - schizophrenic