Cytarabine dose of 36 g/m(2) compared with 12 g/m(2) within first consolidation in acute myeloid leukemia: results of patients enrolled onto the prospective randomized AML96 study.
Author(s): Schaich M, Rollig C, Soucek S, Kramer M, Thiede C, Mohr B, Oelschlaegel U, Schmitz N, Stuhlmann R, Wandt H, Schafer-Eckart K, Aulitzky W, Kaufmann M, Bodenstein H, Tischler J, Ho A, Kramer A, Bornhauser M, Schetelig J, Ehninger G
Affiliation(s): Medizinische Klinik I, Universitatsklinikum C.G. Carus, Dresden, Germany. firstname.lastname@example.org
Publication date & source: 2011-07-01, J Clin Oncol., 29(19):2696-702. Epub 2011 May 23.
Publication type: Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
PURPOSE: To assess the optimal cumulative dose of cytarabine for treatment of young adults with acute myeloid leukemia (AML) within a prospective multicenter treatment trial. PATIENTS AND METHODS: Between 1996 and 2003, 933 patients (median age, 47 years; range 15 to 60 years) with untreated AML were randomly assigned at diagnosis to receive cytarabine within the first consolidation therapy at either a intermediate-dose of 12 g/m(2) (I-MAC) or a high-dose of 36 g/m(2) (H-MAC) combined with mitoxantrone. Autologous hematopoietic stem-cell transplantation or intermediate-dose cytarabine (10 g/m(2)) were offered as second consolidation. Patients with a matched donor could receive an allogeneic transplantation in a risk-adapted manner. RESULTS: After double induction therapy including intermediate-dose cytarabine (10 g/m(2)), mitoxantrone, etoposide, and amsacrine, complete remission was achieved in 66% of patients. In the primary efficacy analysis population, a consolidation with either I-MAC or H-MAC did not result in significant differences in the 5-year overall (30% v 33%; P = .77) or disease-free survival (37% v 38%; P = .86) according to the intention-to-treat analysis. Besides a prolongation of neutropenia and higher transfusion demands in the H-MAC arm, rates of serious adverse events were comparable in the two groups. CONCLUSION: In young adults with AML receiving intermediate-dose cytarabine induction, intensification of the cytarabine dose beyond 12 g/m(2) within first consolidation did not improve treatment outcome.