Background A complete remission is essential for prolongingsurvival in patients with acute myeloid leukemia (AML). Daunorubicinis a cornerstone of the induction regimen, but the optimal doseis unknown. In older patients, it is usual to give daunorubicinat a dose of 45 to 50 mg per square meter of body-surface area.
Methods Patients in whom AML or high-risk refractory anemiahad been newly diagnosed and who were 60 to 83 years of age(median, 67) were randomly assigned to receive cytarabine, ata dose of 200 mg per square meter by continuous infusion for7 days, plus daunorubicin for 3 days, either at the conventionaldose of 45 mg per square meter (411 patients) or at an escalateddose of 90 mg per square meter (402 patients); this treatmentwas followed by a second cycle of cytarabine at a dose of 1000mg per square meter for 6 days. The primary end point was event-freesurvival.
Results The complete remission rates were 64% in the group thatreceived the escalated dose of daunorubicin and 54% in the groupthat received the conventional dose (P=0.002); the rates ofremission after the first cycle of induction treatment were52% and 35%, respectively (P<0.001). There was no significantdifference between the two groups in the incidence of hematologictoxic effects, 30-day mortality (11% and 12% in the two groups,respectively), or the incidence of moderate, severe, or life-threateningadverse events (P=0.08). Survival end points in the two groupsdid not differ significantly overall, but patients in the escalated-treatmentgroup who were 60 to 65 years of age, as compared with the patientsin the same age group who received the conventional dose, hadhigher rates of complete remission (73% vs. 51%), event-freesurvival (29% vs. 14%), and overall survival (38% vs. 23%).
From Erasmus University Medical Center, Rotterdam (B.L., P.S., M.J.-L.); the Department of Hematology, Free University Medical Center, Amsterdam (G.J.O.); the HOVON Data Center and Department of Trials and Statistics, Erasmus University Medical Center, Rotterdam (W.P.); University Medical Center, Maastricht (H.C.S.); Amsterdam University Medical Center, Amsterdam (B.J.B.); University Medical Center, Groningen (E.V.); Isala Hospital, Zwolle (M.M.K.); and University Medical Center, Utrecht (L.F.V.) — all in the Netherlands; Hôpital Mont Godinne, Yvoir (C.G.); Hôpital St. Luc, Brussels (A.F.); and University Hospital Gasthuisberg, Leuven (J.M., G.V.) — all in Belgium; University Hospital, Bonn (M.L.-T.); the Department of Internal Medicine III, University-Hospital, Mainz (J.B.); and the Department of Internal Medicine III, University of Ulm, Ulm (H.D.) — all in Germany; and University Hospital, Basel (A.G.); and Inselspital, Bern (T.P.) — both in Switzerland.