title: 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.affiliation: Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bourquin
authors.forename: Michael N
authors.initials: MN
authors.lastname: Dworzak
authors.forename: Gudrun
authors.initials: G
authors.lastname: Fleischhack
authors.forename: Norbert
authors.initials: N
authors.lastname: Graf
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kremens
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehrnbecher
authors.forename: Christine
authors.initials: C
authors.lastname: von Neuhoff
authors.forename: Jörg
authors.initials: J
authors.lastname: Ritter
authors.forename: Annette
authors.initials: A
authors.lastname: Sander
authors.forename: André
authors.initials: A
authors.lastname: Schrauder
authors.forename: Arend
authors.initials: A
authors.lastname: von Stackelberg
authors.forename: Jan
authors.initials: J
authors.lastname: Starý
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
mesh_terms: D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008081:Liposomes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D015999:Multivariate Analysis; D016609:Neoplasms, Second Primary / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D015255:Idarubicin; D003630:Daunorubicin