A phase I trial of combination chemotherapy employing carboplatin, vinca alkaloids, with or without bleomycin in patients with advanced malignant tumors.

A Phase I trial of three carboplatin-based combination chemotherapy regimens was conducted. These included: carboplatin plus vindesine; carboplatin, vindesine, plus bleomycin; and, carboplatin plus vinblastine. Carboplatin was administered every 28 days as an intravenous bolus. The initial dose was 150 mg/m2 and doses were escalated by 50 mg/m2 in each successive group of patients. Vindesine was given at a dose of 3 mg/m2 weekly for 5 doses, then every other week thereafter. Bleomycin, 10 units/m2 IV bolus, was followed by 10 units/m2/day infusion for 4 days (3-7 and 31-35). Vinblastine was given at 5 mg/m2 every other week. Doses of vindesine, vinblastine, and bleomycin were not escalated. The maximum tolerated dose (MTD) of the carboplatin, vindesine +/- bleomycin regimens was reached at a carboplatin dose of 250 mg/m2 and the MTD was influenced by the weekly vindesine in the initial 4 weeks of therapy. The MTD of the carboplatin and vinblastine regimen was reached at a carboplatin dose of 500 mg/m2. Dose-limiting toxicity of all three regimens was leukopenia. Although nonhematological toxicity of the carboplatin and vinblastine regimen included peripheral neuropathy and emesis, therapy was easily administered in an outpatient setting. The recommended Phase II dose of carboplatin is 450 mg/m2 in combination with vinblastine at this dose and schedule for previously untreated patients. Twelve patients demonstrated major responses with the various regimens including 5 of 24 patients with adenocarcinoma of the upper gastrointestinal tract.