Feasibility study of combining metronidazole with chemotherapy.
Metronidazole, 1.5 g/sq m, was administered p.o. to patients with advanced malignancies 12 hr and 1 hr before and 6 hr and 24 hr after each of adriamycin, BCNU, and mitomycin-C. Doses of adriamycin varied from 50 to 90 mg/sq m. At an adriamycin dose of 75 mg/sq m, the median granulocyte nadir was 900/microliters and the median platelet nadir was 240,000/microliters. No enhancement of stomatitis or cardiotoxicity was noted at the doses studied. Doses of BCNU varied from 145 to 265 mg/sq m. At a BCNU dose of 240 mg/sq m, the median granulocyte nadir was 2600/microliters and the median platelet nadir was 102,000/microliters. Two patients developed hypotension that may have been due to a metronidazole-alcohol interaction. Doses of mitomycin-C varied from 10 to 20 mg/sq m. At a mitomycin-C dose of 20 mg/sq m, the median granulocyte nadir was 1300/microliters and the median platelet nadir was 81,000/microliters. Four of 40 patients developed pulmonary toxicity and one developed renal toxicity. Of 11 evaluable patients treated on the adriamycin regimen, 4 responded and 5 stabilized. With BCNU, 7 of 17 responded and 2 stabilized. With mitomycin-C, 2 of 32 responded and 12 stabilized. Overall, 4 of 8 patients with squamous cell carcinoma or adenocarcinoma of the lung attained partial remissions and one had a minor response. Using this metronidazole dose schedule, phase II studies are being conducted with adriamycin, 75 mg/sq m, in squamous cell and adenocarcinomas of the head and neck; with BCNU, 240 mg/sq m, in glioblastomas and squamous cell and adenocarcinoma of the lung; and with mitomycin-C, 20 mg/sq m, in adenocarcinomas of the breast and colon.
D000230:Adenocarcinoma / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy; D001943:Breast Neoplasms / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D005910:Glioma / Q000188:drug therapy; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006801:Humans; D007958:Leukocyte Count; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage / Q000009:adverse effects; D009369:Neoplasms / Q000188:drug therapy*; D010865:Pilot Projects; D010976:Platelet Count
D000970:Antineoplastic Agents; D008937:Mitomycins; D008795:Metronidazole; D016685:Mitomycin; D004317:Doxorubicin; D002330:Carmustine