Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine

The treatment of older patients with acute myeloid leukemia (AML) remains u nsatisfactory, with complete remission (CR) achieved in only approximately 50% and long-term disease-free survival in 10% to 20%. Three hundred eighty -eight patients (60 years of age and older) with newly diagnosed de novo AM L were randomly assigned to receive placebo (P) or granulocyte-macrophage c olony-stimulating factor (GM-CSF) or GM in a double-blind manner, beginning 1 day after the completion of 3 days of daunorubicin and 7 days of cytarab ine therapy. No differences were found in the rates of leukemic regrowth, C R, or infectious complications in either arm. Of 205 patients who achieved CR, 169 were medically well and were randomized to receive cytarabine alone or a combination of cytarabine and mitoxantrone. With a median follow-up o f 7.7 years, the median disease-free survival times were 11 months and 10 m onths for those randomized to cytarabine or cytarabine/ mitoxantrone, respe ctively. Rates of relapse, excluding deaths in CR, were 77% for cytarabine and 82% for cytarabine/ mitoxantrone. Induction randomization had no effect on leukemic relapse rate or remission duration in either postremission arm . Because cytarabine/mitoxantrone was more toxic and no more effective than cytarabine, it was concluded that this higher-dose therapy had no benefit in the postremission management of older patients with de novo AML. These r esults suggest the need to develop novel therapeutic strategies for these p atients.