The effect of tamoxifen and cisplatin on the disease-free and overall survival of patients with high risk malignant melanoma.
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The adjuvant treatment of high-risk malignant melanoma remains problematic. Previously we reported moderate success in the treatment of metastatic disease using tamoxifen, cisplatin, dacarbazine and carmustine. Based upon data that suggested tamoxifen and cisplatin were the active agents in this regimen, we initiated a phase II trial of this combination in the adjuvant setting. We treated 153 patients with 4 cycles of tamoxifen (160 mg day(-1), days 1-7) and cisplatin (100 mg m(-2), day 2) for 28-day intervals. Patients received an anti-nausea regimen of dexamethasone with ondansetron or granisetron. During the first 2 years of follow-up, patients were evaluated every 2 months with a history, physical exam, laboratory work and computed tomography scans of the chest, abdomen and pelvis every 4 months. Thereafter, patients were evaluated every 3 months and radiographic studies were performed if necessary. Currently, with a median follow-up of 36 months, the disease-free survival (DFS) is 68.4% and overall survival (OS) is 84.5%. Kaplan-Meier analysis predicts a 5-year DFS of 62% with an OS of 79%. Relapses after 20 months have been rare. No effect of gender or number of positive lymph nodes was noted, however, stage of disease prior treatment was a factor. The major toxicity proved to be gastrointestinal in nature with nausea the most prevalent symptom. Minimal renal, haematologic and neurologic toxicity occurred. These preliminary results suggest that there is a positive impact of tamoxifen and cisplatin on both the DFS and OS of high-risk malignant melanoma patients. The 5-year projected DFS and OS compare favourably with those reported for the ECOG 1684 trial and warrant confirmation in a prospective randomized trial. (+info)
Comparison of the neurokinin-1 antagonist GR205171, alone and in combination with the 5-HT3 antagonist ondansetron, hyoscine and placebo in the prevention of motion-induced nausea in man.
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AIMS: In man a neurokinin-1 (NK1) receptor antagonist has previously been shown to be ineffective in the prevention of motion-induced nausea. The antiemetic efficacy of NK1 receptor antagonists against chemotherapy-induced emesis is, however, enhanced when combined with a 5-HT3 receptor antagonist. Hence the efficacy of the NK1 antagonist GR205171 in combination with the 5-HT3 antagonist ondansetron (Zofrantrade mark) was assessed in motion-induced nausea. METHODS: GR205171 25 mg i.v., with and without concomitant administration of ondansetron 8 mg i.v., and hyoscine hydrobromide 0. 6 mg orally (positive control) were compared with placebo in a model of motion-induced nausea. The study was performed to a four-period, randomized, balanced, double-blind, crossover design in 16 healthy subjects. The end-point was the exposure to the motion stimulus required to produce moderate nausea in the subjects. RESULTS: The motion stimulus required to produce moderate nausea was significantly greater for the positive control than placebo (P < 0. 001). There was no significant difference between either GR205171 or GR205171 plus ondansetron and placebo (P = 0.648 and 0.342, respectively). CONCLUSIONS: The enhancement of NK1 receptor antagonist antiemetic activity through combination with a 5-HT3 receptor antagonist is not replicated in motion-induced nausea. (+info)
The use of haloperidol for treatment of postoperative nausea and vomiting--a double-blind placebo-controlled trial.
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Sixty-two postoperative patients were admitted to a double-blind study to compare the therapeutic effectiveness of a single intramuscular injection of 1 mg of haloperidol with that of a placebo for the relief of vomiting and nausea following surgical procedures. Significantly fewer patients continued to vomit or experience nausea in the haloperidol-treatment group than in the placebo-treatment group. No statistically or clinically significant change in vital signs occurred in the haloperidol-treatment group. No serious side effect occurred in either group. (+info)
Double-blind, randomized, parallel-group study on the efficacy and safety of oral granisetron and oral ondansetron in the prophylaxis of nausea and vomiting in patients receiving hyperfractionated total body irradiation.
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The efficacy and safety of granisetron and ondansetron for the prophylaxis of nausea and vomiting resulting from hyperfractionated total body irradiation (TBI) were assessed. Thirty-four patients randomly received double-blind, oral granisetron (2 mg, 1 h before first daily fraction of radiation) or ondansetron (8 mg, 1.5 h prior to each fraction of TBI). Ninety patients who received the same TBI regimen prior to bone marrow transplantation (BMT), but no 5-HT3-receptor antagonist, were identified and comprised the historical control group. By design, this study was only powered to show a difference between each of the active treatment groups and the historical control group. Significantly more patients given granisetron (33.3%) or ondansetron (26.7%) had zero emetic episodes over 4 days, the primary efficacy end point, than those in the historical control group (0%) (P < 0.01; intent-to-treat). Secondary efficacy end points were also evaluated. During the first 24 h, significantly more patients taking granisetron (61.1%) or ondansetron (46.7%) had zero emetic episodes than patients in the historical control group (6.7%) (P < 0.01). Complete emetic control (no emesis or rescue antiemetic) over 4 days was more frequent in patients taking granisetron (27.8%) or ondansetron (26.7%) compared with the historical control group (0%) (P < 0.01). Significantly fewer patients taking granisetron (18/18), but not those taking ondansetron (12/15), experienced more than five emetic episodes during the 4 days of the study compared with the historical control group (40/90; P < 0.01). Oral granisetron and ondansetron are safe and effective for the prevention of nausea and vomiting resulting from TBI. (+info)
Comparison of oral ampicillin and doxycycline in the treatment of uncomplicated gonorrhoea.
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An account is given of a computer-processed 1-year study comprising 1,124 patients (625 males and 499 females) with uncomplicated gonorrhoea. Alternate patients were treated with either two oral doses of 1 g. ampicillin 5 hours apart, or 0.3 g. doxycycline in a single oral dose. Ampicillin remained as efficacious as in 1968 to 1970, in both males and females, in whom the failure rates were 1.1 and 1 per cent. respectively. After doxycycline the failure rate was 8.1 per cent. in males, 5.7 per cent. in females, and 7.1 per cent. overall. Ampicillin was significantly better than doxycycline in the treatment of men (P less than 0.001) as well as of women (0.05 greater than P greater than 0.01). 89.7 per cent. (29/29) of the relapses in doxycycline-treated patients occurred in those harbouring strains sensitive to tetracycline. Sensitivity to doxycycline followed the pattern of tetracycline sensitivity. Thus sensitivity tests with these antibiotics provided no practical aid to therapy. The high incidence of nausea and vomiting in patients treated with doxycycline (12 per cent.) makes it inadvisable to increase the dose; instead, multiple doses are necessary to obtain satisfactory results. There were very few adverse reactions to ampicillin; a rash occurred in only three patients (0.5 per cent.). In the group treated with doxycycline, 31.5 per cent. of the patients infected by streptomycin-resistant strains relapsed compared with only 1.8 per cent. of patients infected by streptomycin-sensitive strains. This difference is highly significant (P less than 0.001). Thus the sensitivity of gonococcal strains to streptomycin in vitro may serve as a valuable guide to the likely outcome of treatment with tetracyclines. (+info)
Feprazone, a new anti-inflammatory agent. Studies of potency and gastrointestinal tolerance.
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Two studies are reported; a double-blind cross-over trial of feprazone 600 mg daily and aspirin 3.6 g daily in the treatment of rheumatoid arthritis, and an uncontrolled open study of gastrointestinal tolerance in twenty rheumatoid arthritis patients with known intolerance to other drugs. The first study showed that feprazone was significantly superior to aspirin in all the parameters tested. In the second study all twenty patients showed an improvement of their gastrointestinal symptoms, nineteen reporting no symptoms at all when taking the new preparation. (+info)
Metoclopramide and pimozide in Parkinson's disease and levodopa-induced dyskinesias.
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Metoclopramide is an antiemetic drug which occasionally produced acute dystonic reactions. Although known to interfere with central dopamine mechanisms, it is frequently used in Parkinson's disease to prevent levodopa-induced nausea and vomiting. In this study metoclopramide did not increase Parkinsonism or reduce levodopa-induced involuntary movements in patients with Parkinson's disease. Pimozide, by contrast, increased Parkinsonism and reduced involuntary movements. The capacity of metoclopramide to produce acute dyskinesias while being apparently free of Parkinsonism effects is pharmacologically unique and differentiates this drug from the phenothiazines and butyrophenones. (+info)
DX-8951f, a hexacyclic camptothecin analog, on a daily-times-five schedule: a phase I and pharmacokinetic study in patients with advanced solid malignancies.
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PURPOSE: To assess the feasibility of administering DX-8951f (exatecan mesylate), a water-soluble, camptothecin analog, as a 30-minute intravenous infusion daily for 5 days every 3 weeks, determine the maximum-tolerated dose (MTD) and pharmacokinetic (PK) behavior of DX-8951f, and seek preliminary evidence of anticancer activity. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of DX-8951f. After three patients were treated at the first dose level, doses were to be escalated in increments of 100%, using a single patient at each dose level unless moderate toxicity was observed. The MTD, defined as the highest dose level at which the incidence of dose-limiting toxicity did not exceed 20%, was calculated separately for minimally pretreated (MP) and heavily pretreated (HP) patients. The PK and excretory profiles of DX-8951, the anhydrous form of DX-8951f, were also characterized. RESULTS: Thirty-six patients were treated with 130 courses of DX-8951f at six dose levels ranging from 0.1 to 0.6 mg/m(2)/d. Brief, noncumulative neutropenia was the most common toxicity observed. Severe myelosuppression (neutropenia that was protracted and/or associated with fever and/or severe thrombocytopenia) was consistently experienced by HP and MP patients at doses exceeding 0.3 and 0.5 mg/m(2)/d, respectively. Nonhematologic toxicities (nausea, vomiting, and diarrhea) were also observed, but these effects were rarely severe. Objective antitumor activity included partial responses in one patient each with platinum-resistant extrapulmonary small-cell and fluoropyrimidine- and irinotecan-resistant colorectal carcinoma, and minor responses in patients with prostate, hepatocellular, thymic, primary peritoneal, and irinotecan-resistant colorectal carcinomas. The PKs of total DX-8951 were linear and well fit by a three-compartment model. CONCLUSION: The recommended doses for phase II studies of DX-8951f as a 30-minute infusion daily for 5 days every 3 weeks are 0.5 and 0.3 mg/m(2)/d for MP and HP patients, respectively. The characteristics of the myelosuppressive effects of DX-8951f, paucity of severe nonhematologic toxicities, and antitumor activity against a wide range of malignancies warrant broad disease-directed evaluations of DX-8951f on this schedule. (+info)