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 treat ed in this phase I study of menogaril (7-con-O-methylnogarol), a nogal amycin anthracycline derivative. Doses ranged from 50 mg/m(2)/day to 1 30 mg/m(2)/day, administered daily for 5 days. Pharmacokinetic studies were performed at each dose level and confirmed the findings of pharm acokinetic data derived from previous studies in patients with solid t umors. All patients experienced grade 4 hematologic toxicity and the d ose limiting toxicity was mucositis. Two patients, one with acute myel oid leukemia and one with acute lymphoid leukemia, achieved complete r esponses. The AML complete response lasted 10 months and the ALL patie nt died in CR at 2+ months. Both patients were treated at a dose of 10 0 mg/m(2)/day for five days. At this dose, a second induction or conso lidation course could be given without severe mucositis, and this is t he dose recommended for further phase II studies in leukemia using thi s schedule.