What Is the Best Daunorubicin Dose and Schedule for Acute Myeloid Leukemia Induction?

Abstract

Daunorubicin dose intensification for induction in acute myeloid leukemia has been reported as an effective strategy in recent trials to improve patient outcomes without worsening treatment-related toxicity. Based on available evidence, 90mg/m2 of daunorubicin given for three consecutive days (cumulative dose 270mg/m2) as a part of the "7+3" induction regimen along with cytarabine is the most effective dose to achieve a complete remission as well as improve survival in patients who can tolerate it. This should be considered strongly in younger patients (less than 65years of age and especially in those less than 50years) irrespective of cytogenetic risk (likely more beneficial for favorable and intermediate risk) or molecular mutations (definitely in those with NPM1 or FLT3-ITD mutations). Among older acute myeloid leukemia (AML) patients (>65years), using a higher dose of daunorubicin may not improve survival. It is unclear if daunorubicin at 60mg/m2 for 3days is as efficacious as the 90mg/m2 dose but may be used when there are concerns about tolerability of the higher dose. Although 90mg/m2 has no more adverse effects compared to 45mg/m2 of daunorubicin, increasing dosage beyond a cumulative dose of 330mg/m2 is detrimental due to increase in early mortality. Idarubicin 12mg/m2 for 3days is an alternative with the possibility of better long-term outcomes. Elderly patients with AML and those with unfavorable cytogenetics, secondary, or treatment-related disease remain challenging to treat. All patients should be treated on clinical trials when available.