A randomized trial conducted by the ECOG showed that intensification of induction therapy using a high daily dose of daunorubicin (90 mg/m2/d x 3d) improved both complete remission (CR) rate and survival duration compared with those of young adults with acute myeloid leukemia (AML) receiving standard daunorubicin dose (45 mg/m2/d x 3d) (Fernandez HF et al. N Engl J Med 2009;361:1249). We also conducted a randomized trial comparing two different doses of daunorubicin as induction chemotherapy in young adults with AML (Lee JH et al. Blood 2011;118:3832).Methods
Of 383 patients who were analyzed, 189 received standard-dose daunorubicin (SD-DN, 45 mg/m2/d x 3d) and 194 received high-dose daunorubicin (HD-DN, 90 mg/m2/d x 3d) in addition to cytarabine (200 mg/m2/d x 7d) to induce CR.Results
The CR rates were 72.0% in SD-DN arm and 82.5% in HD-DN arm. At a median follow-up time of 52.6 months, overall (OS) and event-free (EFS) survival were higher in HD-DN arm than in SD-DN arm (OS, 46.8% versus 34.6%; EFS, 40.8% versus 28.4%). Differences in CR rate and both OS and EFS remained significant after adjustment for other variables (CR, HR, 1.802, P = 0.024; OS, HR, 0.739, P = 0.032; EFS, HR, 0.774, P = 0.048).Conclusions
Given the results of both our study and the ECOG work, high-dose daunorubicin (90 mg/m2/d) for 3 days should be the future standard of care for induction of patients with AML. However, it is not known whether a dose of 90 mg/m2/d is superior to a dose of 45–90 mg/m2/day. It is also necessary to compare the effects of high-dose daunorubicin with that of other agents, especially idarubicin. For these reasons, we began another randomized trial comparing two induction regimens in young adults with AML: high-dose daunorubicin (90 mg/m2/d x 3d) versus idarubicin (12 mg/m2/d x 3d) in addition to cytarabine (200 mg/m2/d x 7d). This study is now recruiting patients and the results of interim analysis will be presented at the 10th annual meeting of Japanese Society of Medical Oncology.