Bradstock, KF and Link, E and Iulio, JD and Szer, J and Marlton, P and Wei, AH and Enno, A and Schwarer, A and Lewis, ID and Da Rozario, J and Coyle, L and Cull, G and Campbell, P and Leahy, MF and Hahn, U and Cannell, P and Tiley, C and Lowenthal, RM and Moore, J and Cartwright, K and Cunningham, I and Taper, J and Grigg, A and Roberts, AW and Benson, W and Hertzberg, M and Deveridge, S and Rowlings, P and Mills, AK and Gill, D and Bardy, P and Campbell, L and Seymour, JF, on behalf of the Australasian Leukaemia & Lymphoma Group, Idarubicin dose escalation during consolidation therapy for adult acute myeloid leukemia, Journal of Clinical Oncology, 35, (15) pp. 1678-1685. ISSN 0732-183X (2017) [Refereed Article]
Copyright 2017 American Society of Clinical Oncology
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.
|Item Type:||Refereed Article|
|Keywords:||acute mylenoid leukemia, AML, idarubicin, consolidation therapy, induction therapy, daunorubicin|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Oncology and carcinogenesis|
|Research Field:||Oncology and carcinogenesis not elsewhere classified|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Lowenthal, RM (Professor Ray Lowenthal)|
|Web of Science® Times Cited:||11|
|Deposited By:||Menzies Institute for Medical Research|
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