PHASE-I TRIAL OF MENOGARIL ADMINISTERED AS AN INTERMITTENT DAILY INFUSION FOR 5 DAYS

  • 1 June 1986
    • journal article
    • research article
    • Vol. 70  (6) , 721-725
Abstract
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 .times. 5, with escalation in subsequent cohorts of patients to 56 mg/m2/day .times. 5. Neutropenia was dose dependent and dose limiting. At 56 mg/m2/day .times. 5, the median wbc count nadir was 1100/.mu.l, and two of four patients were hospitalized for fever and suspected bacteremia. At 50 mg/m2/day .times. 5, the wbc count nadir was 2300/.mu.l. 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.