Mitoxantrone and ara-C in previously treated patients with acute myelogenous leukemia.

Mitoxantrone is a synthetic aminoanthraquinone we have previously reported to be effective for patients with acute leukemia in relapse. We presently report the results of a trial of mitoxantrone in combination with cytosine arabinoside (ara-C) in patients with refractory or relapsed acute myelocytic leukemia (AML). Forty-nine patients, 24 males and 25 females, with a median age of 56, of whom 32 were in first relapse, four were in second relapse, and 13 had primarily refractory AML, were treated with mitoxantrone 10 mg/m2 daily for 3 days and ara-C 100 mg/m2 daily by continuous infusion for 7 days. Twenty patients (62.5%) with first relapse AML achieved M1 marrow, whereas only two of 13 patients with refractory AML did; none of four patients with more than one prior remission responded. Marrow recovery was observed in a median of 32 days. Remissions were maintained with monthly ara-C plus mitoxantrone alternating with ara-C plus 6-TG; median duration of remission was 8 months and two patients are in continuing remission at 8 and 16 months. Treatment was well tolerated, with minimal nausea and vomiting, diarrhea, drug-induced mucositis. Treatment-related cardiac toxicity was not observed. Transient hepatic dysfunction was observed in greater than 50% of courses. Mitoxantrone plus ara-C is an active combination with great promise for the therapy of previously untreated patients with AML.