Idarubicin dose escalation during consolidation therapy for adult acute myeloid leukemia

Bradstock, KF; Link, E; Di Iulio, J; Szer, J; Marlton, P; Wei, AH; Enno, A; Schwarer, A; Lewis, ID; D&#39;Rozario, J; Coyle, L; Cull, G; Campbell, P; Leahy, MF; Hahn, U; Cannell, P; Tiley, C; Lowenthal, RM; Moore, J; Cartwright, K; Cunningham, I; Taper, J; Grigg, A; Roberts, AW; Benson, W; Hertzberg, M; Deveridge, S; Rowlings, P; Mills, AK; Gill, D; Bardy, P; CAMPBELL, L; Seymour, JF; Australasian Leukaemia Lymphoma Group,

Author(s): Bradstock, KF; Link, E; Di Iulio, J; Szer, J; Marlton, P; Wei, AH; Enno, A; Schwarer, A; Lewis, ID; D'Rozario, J; Coyle, L; Cull, G; Campbell, P; Leahy, MF; Hahn, U; Cannell, P; Tiley, C; Lowenthal, RM; Moore, J; Cartwright, K; Cunningham, I; Taper, J; Grigg, A; Roberts, AW; Benson, W; Hertzberg, M; Deveridge, S; Rowlings, P; Mills, AK; Gill, D; Bardy, P; CAMPBELL, L; Seymour, JF; Australasian Leukaemia Lymphoma Group,;
Details: Publication Year 2017-05-20,Volume 35,Issue #15,Page 1678-1685
Journal Title: J Clin Oncol
Publication Type: Journal Article
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: ASCO
Research Division(s): Cancer And Haematology
PubMed ID: 28368672
Publisher's Version: https://doi.org/10.1200/JCO.2016.70.6374
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2017-06-26 02:15:21

Last Modified: 2017-06-26 02:21:48