Idarubicin Dose Escalation During Consolidation Therapy for Adult Acute Myeloid Leukemia
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Published:2017-05-20
Issue:15
Volume:35
Page:1678-1685
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Bradstock Kenneth F.1, Link Emma1, Di Iulio Juliana1, Szer Jeff1, Marlton Paula1, Wei Andrew H.1, Enno Arno1, Schwarer Anthony1, Lewis Ian D.1, D’Rozario James1, Coyle Luke1, Cull Gavin1, Campbell Phillip1, Leahy Michael F.1, Hahn Uwe1, Cannell Paul1, Tiley Campbell1, Lowenthal Ray M.1, Moore John1, Cartwright Kimberly1, Cunningham Ilona1, Taper John1, Grigg Andrew1, Roberts Andrew W.1, Benson Warwick1, Hertzberg Mark1, Deveridge Sandra1, Rowlings Philip1, Mills Anthony K.1, Gill Devinder1, Bardy Peter1, Campbell Lynda1, Seymour John F.1,
Affiliation:
1. Kenneth F. Bradstock and Warwick Benson, Westmead Hospital, University of Sydney; Arno Enno, Sandra Deveridge, and Philip Rowlings, Calvary Mater Newcastle Hospital, Newcastle; Luke Coyle, Royal North Shore Hospital, St Leonards; Campbell Tiley, Central Coast Health, Gosford; John Moore, St Vincent's Hospital; Mark Hertzberg, Prince of Wales Hospital, Sydney; Kimberly Cartwright, Wollongong Hospital, Wollongong; Ilona Cunningham, Concord Repatriation General Hospital, Concord; John Taper, Nepean Hospital...
Abstract
Purpose Higher doses of the anthracycline daunorubicin during induction therapy for acute myeloid leukemia (AML) have been shown to improve remission rates and survival. We hypothesized that improvements in outcomes in adult AML may be further achieved by increased anthracycline dose during consolidation therapy. Patients and Methods Patients with AML in complete remission after induction therapy were randomly assigned to receive two cycles of consolidation therapy with cytarabine 100 mg/m2 daily for 5 days, etoposide 75 mg/m2 daily for 5 days, and idarubicin 9 mg/m2 daily for either 2 or 3 days (standard and intensive arms, respectively). The primary end point was leukemia-free survival (LFS). Results Two hundred ninety-three patients 16 to 60 years of age, excluding those with core binding factor AML and acute promyelocytic leukemia, were randomly assigned to treatment groups (146 to the standard arm and 147 to the intensive arm). Both groups were balanced for age, karyotypic risk, and FLT3–internal tandem duplication and NPM1 gene mutations. One hundred twenty patients in the standard arm (82%) and 95 patients in the intensive arm (65%) completed planned consolidation ( P < .001). Durations of severe neutropenia and thrombocytopenia were prolonged in the intensive arm, but there were no differences in serious nonhematological toxicities. With a median follow-up of 5.3 years (range, 0.6 to 9.9 years), there was a statistically significant improvement in LFS in the intensive arm compared with the standard arm (3-year LFS, 47% [95% CI, 40% to 56%] v 35% [95% CI, 28% to 44%]; P = .045). At 5 years, the overall survival rate was 57% in the intensive arm and 47% in the standard arm ( P = .092). There was no evidence of selective benefit of intensive consolidation within the cytogenetic or FLT3–internal tandem duplication and NPM1 gene mutation subgroups. Conclusion An increased cumulative dose of idarubicin during consolidation therapy for adult AML resulted in improved LFS, without increased nonhematologic toxicity.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Cited by
14 articles.
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