Phase I trial of menogaril administered as an intermittent daily infusion for 5 days.
Menogaril, a semisynthetic derivative of nogalomycin, was brought to phase I clinical testing in patients with refractory solid tumors. Twenty-seven patients received 50 evaluable courses. Menogaril was given as a 1-2-hour iv infusion on 5 consecutive days, with courses repeated every 4 weeks, provided there was reversal of all drug-related toxic effects. The starting dose was 3.5 mg/m2/day X 5, with escalations in subsequent cohorts of patients to 56 mg/m2/day X 5. Neutropenia was dose dependent and dose limiting. At 56 mg/m2/day X 5, the median wbc count nadir was 1100/microliter, and two of four patients were hospitalized for fever and suspected bacteremia. At 50 mg/m2/day X 5, the wbc count nadir was 2300/microliter. Platelet toxicity was less severe. Nonhematologic toxicity consisted primarily of local urticaria and moderate to severe phlebitis at the infusion site, which were dose dependent and lasted up to 6 weeks. For phase II studies, the recommended dose of menogaril is 50 mg/m2/day for 5 consecutive days administered as a 2-hour intermittent infusion, repeated every 28 days.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003630:Daunorubicin / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007263:Infusions, Parenteral; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D017290:Menogaril; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009621:Nogalamycin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D017290:Menogaril; D009621:Nogalamycin; D003630:Daunorubicin