Phase I clinical and pharmacokinetic study of menogaril (7-con-O-methylnogarol) in previously treated patients with acute leukemia.

Fifteen patients with relapsed or refractory acute leukemia were treated in this phase I study of menogaril (7-con-O-methylnogarol), a nogalamycin anthracycline derivative. Doses ranged from 50 mg/m2/day to 130 mg/m2/day, administered daily for 5 days. Pharmacokinetic studies were performed at each dose level and confirmed the findings of pharmacokinetic data derived from previous studies in patients with solid tumors. All patients experienced grade 4 hematologic toxicity and the dose limiting toxicity was mucositis. Two patients, one with acute myeloid leukemia and one with acute lymphoid leukemia, achieved complete responses. The AML complete response lasted 10 months and the ALL patient died in CR at 2+ months. Both patients were treated at a dose of 100 mg/m2/day for five days. At this dose, a second induction or consolidation course could be given without severe mucositis, and this is the dose recommended for further phase II studies in leukemia using this schedule.