Fernandez et al on behalf of the SWOG group (ECOG1900 trial) studied adults aged 17 to 60 (median age 48), combining cytarabine 100 mg/m2 by short IV infusion with daunorubicin on day 1 to 3 either at 45 mg/m2 or 90 mg/m2. Notably a second induction at standard dose was given if residual blasts were detected in the bone marrow on day 12 to 14. Both CR (70.6 vs 57.3%) and OS (23.7 vs 15.7 months) were superior in the high dose group at a follow-up of 25 months. The greatest difference in survival was observed in patients under the age of 50 years and those with intermediate risk cytogenetics. This group has subsequently published an updated analysis of this cohort showing a significant reduction in death (HR 0.74, P= 0.002) for patients who received daunorubicin at 90 mg/m2 vs 45 mg/m2 at a median follow up of 80 months. Furthermore, significant survival benefit continued to be seen in patients under 50 years and intermediate cytogenetic risks but also extended across all cytogenetic and molecular risk groups, especially NPM1 and DNMT3A mutations.r
Kaplan-Meier Estimates of Overall Survival
© NEJM 2009
Lee et al followed a similar schema for a lower total cohort of patients, the only variance being cytarabine 200 mg/m2 by continuous infusion. Again, CR rates (82.5 vs 72%) and OS (46.8 vs 34.6%) were superior in the higher dose arm but at a follow up of 52 months. In this study, which featured a longer follow-up than the ECOG study, also confirmed that the survival benefit of high dose daunorubicin was most evident in the intermediate cytogenetic risk group.r
Survival differences between the standard-dose(SD-DN) and high-dose (HD-DN) arms.
© Blood 2011
Lowenberg et al studied a large group of patients with AML aged 60 to 83 (median age 67), with randomisation as described above. In this study patients could receive a second induction following (“7+3”) which consisted of cytarabine at 1 g/m2. CR rates were 52% vs 35% after the first induction, in favour of higher dose daunorubicin. OS did not differ for the group as a whole, but in the age group 60 to 65 was 38% vs 23% in favour of higher dose daunorubicin. An OS was also pronounced for patients with core binding factor abnormalities.r
Effect of Remission-Induction Chemotherapy with an Escalated Dose of Daunorubicin versus a Conventional Dose on Event-free Survival and Overall Survival in Patients 60 years of Age or Older with Acute Myeloid Leukemia.
© NEJM 2009