Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004.

Abstract

Outcomes of patients with acute myeloid leukemia (AML) improve significantly by intensification of induction. To further intensify anthracycline dosage without increasing cardiotoxicity, we compared potentially less cardiotoxic liposomal daunorubicin (L-DNR) to idarubicin at a higher-than-equivalent dose (80 vs 12 mg/m(2) per day for 3 days) during induction. In the multicenter therapy-optimization trial AML-BFM 2004, 521 of 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 [EFS] 59% ± 3% vs 53% ± 3%, Plogrank = .25; cumulative incidence of relapse 29% ± 3% vs 31% ± 3%, P(Gray) = .75), as were EFS results for standard (72% ± 5% vs 68% ± 5%, Plogrank = .47) and high-risk (51% ± 4% vs 46% ± 4%, Plogrank = .45) patients. L-DNR resulted in significantly better probability of EFS in patients with t(8;21). Overall, treatment-related mortality was lower with L-DNR than idarubicin (2/257 vs 10/264 patients, P = .04). Grade 3/4 cardiotoxicity was rare after induction (4 L-DNR vs 5 idarubicin). Only 1 L-DNR and 3 idarubicin patients presented with subclinical or mild cardiomyopathy during follow-up. In conclusion, at the given dose, L-DNR has overall antileukemic activity comparable to idarubicin, promises to be more active in subgroups, and causes less treatment-related mortality. This trial was registered at www.clinicaltrials.gov as #NCT00111345.

• Authors: Ursula Creutzig, Martin Zimmermann, Jean-Pierre Bourquin, Michael N Dworzak, Gudrun Fleischhack, Norbert Graf, Thomas Klingebiel, Bernhard Kremens, Thomas Lehrnbecher, Christine von Neuhoff, Jörg Ritter, Annette Sander, André Schrauder, Arend von Stackelberg, Jan Starý, Dirk Reinhardt
• Journal: Blood (Blood) Vol. 122 Issue 1 Pg. 37-43 (Jul 04 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 23704089 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Liposomes
• Idarubicin
• Daunorubicin

Topics

• Adolescent
• Antibiotics, Antineoplastic (administration & dosage, adverse effects, pharmacokinetics)
• Bone Marrow (drug effects, pathology)
• Child
• Child, Preschool
• Daunorubicin (administration & dosage, adverse effects, pharmacokinetics)
• Dose-Response Relationship, Drug
• Female
• Heart Diseases (chemically induced, mortality)
• Humans
• Idarubicin (administration & dosage, adverse effects, pharmacokinetics)
• Leukemia, Myeloid, Acute (drug therapy, mortality, pathology)
• Liposomes (administration & dosage, pharmacokinetics)
• Male
• Multivariate Analysis
• Neoplasms, Second Primary (pathology)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (pathology)
• Proportional Hazards Models
• Risk Factors
• Treatment Outcome