TY  - JOUR
A1  - Krug, Utz
A1  - Koschmieder, Anja
A1  - Schwammbach, Daniela
A1  - Gerss, Joachim
A1  - Tidow, Nicola
A1  - Steffen, Björn
A1  - Bug, Gesine
A1  - Brandts, Christian Hubertus
A1  - Schaich, Markus
A1  - Röllig, Christoph
A1  - Thiede, Christian
A1  - Noppeney, Richard
A1  - Stelljes, Matthias
A1  - Büchner, Thomas
A1  - Koschmieder, Steffen
A1  - Dührsen, Ulrich
A1  - Serve, Hubert
A1  - Ehninger, Gerhard
A1  - Berdel, Wolfgang E.
A1  - Müller-Tidow, Carsten
T1  - Feasibility of azacitidine added to standard chemotherapy in older patients with acute myeloid leukemia - a randomised SAL pilot study
T2  - PLoS One
N2  - INTRODUCTION: Older patients with acute myeloid leukemia (AML) experience short survival despite intensive chemotherapy. Azacitidine has promising activity in patients with low proliferating AML. The aim of this dose-finding part of this trial was to evaluate feasibility and safety of azacitidine combined with a cytarabine- and daunorubicin-based chemotherapy in older patients with AML.
TRIAL DESIGN: Prospective, randomised, open, phase II trial with parallel group design and fixed sample size.
PATIENTS AND METHODS: Patients aged 61 years or older, with untreated acute myeloid leukemia with a leukocyte count of <20,000/µl at the time of study entry and adequate organ function were eligible. Patients were randomised to receive azacitidine either 37.5 (dose level 1) or 75 mg/sqm (dose level 2) for five days before each cycle of induction (7+3 cytarabine plus daunorubicine) and consolidation (intermediate-dose cytarabine) therapy. Dose-limiting toxicity was the primary endpoint.
RESULTS: Six patients each were randomised into each dose level and evaluable for analysis. No dose-limiting toxicity occurred in either dose level. Nine serious adverse events occurred in five patients (three in the 37.5 mg, two in the 75 mg arm) with two fatal outcomes. Two patients at the 37.5 mg/sqm dose level and four patients at the 75 mg/sqm level achieved a complete remission after induction therapy. Median overall survival was 266 days and median event-free survival 215 days after a median follow up of 616 days.
CONCLUSIONS: The combination of azacitidine 75 mg/sqm with standard induction therapy is feasible in older patients with AML and was selected as an investigational arm in the randomised controlled part of this phase-II study, which is currently halted due to an increased cardiac toxicity observed in the experimental arm.
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28362
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-283620
SN  - 1932-6203
N1  - Copyright: © 2012 Krug et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 7
IS  - (12): e52695
PB  - PLoS
CY  - Lawrence, Kan.
ER  -