AML induction with liposomal daunorubicin (80mg/sqm/d/x3) shows an overall anti-leukemic activity comparable to idarubicin (12mg/m/d/x3).
Liposomal daunorubicin promises to be more active in the subgroup t(8;21) and causes less treatment related toxicity.
Outcome of adult and pediatric patients with AML improved significantly by intensification of induction treatment. To further intensify anthracycline-dosage without increasing cardiotoxicity, we compared the potentially less cardiotoxic liposomal daunorubicin (L-DNR) at a higher than equivalent dose (80mg/m2/day/x3) to idarubicin (12mg/m2/day/x3) during induction. In study AML-BFM 2004, 521/611 pediatric patients (85%) were randomly assigned to L-DNR or idarubicin induction. Five-year results in both treatment arms were similar (overall survival: 76%±3% [L-DNR] vs. 75%±3% [idarubicin], plogrank=.65, event-free survival [pEFS]: 59%±3% vs. 53%±3%, plogrank=.25; cumulative incidence of relapse: 29%±3% vs. 31%±3%, p(Gray)=0.75), as were EFS results for standard (72%±5% vs. 68%±5%, plogrank=.47) and high-risk patients (51%±4% vs. 46%±4%, plogrank=.45). L-DNR resulted in significantly better pEFS in t(8;21) patients. Overall, treatment-related mortality (TRM), was lower in the L-DNR- than in the idarubicin-group (2/257 vs. 10/264 patients, p=.04). Grade III/IV cardiotoxicity was rare after induction (4 L-DNR- vs. 5 idarubicin-patients). Only one L-DNR- and 3 idarubicin-patients presented with subclinical or mild cardiomyopathy during follow-up. We conclude that L-DNR has - at the given dose - an overall anti-leukemic activity comparable to idarubicin, promises to be more active in subgroups, and causes less TRM. These results with high survival rates support its use in the forthcoming AML-BFM trial. ClinicalTrials.gov Identifier: NCT00111345
- Submitted February 12, 2013.
- Accepted April 17, 2013.
- Copyright © 2005 American Society of Hematology