TY  - JOUR
A1  - Röllig, Christoph
A1  - Kramer, Michael
A1  - Gabrecht, Maria
A1  - Hänel, Mathias
A1  - Herbst, Regina
A1  - Kaiser, Ulrich
A1  - Schmitz, Norbert
A1  - Kullmer, Johannes
A1  - Fetscher, Sebastian
A1  - Link, Hartmut
A1  - Mantovani Löffler, Luisa
A1  - Krümpelmann, Ulrich
A1  - Neuhaus, Thomas
A1  - Heits, Frank
A1  - Einsele, Hermann
A1  - Ritter, Barbara
A1  - Bornhäuser, Martin
A1  - Schetelig, Johannes
A1  - Thiede, Carsten
A1  - Mohr, Brigitte
A1  - Schaich, Markus
A1  - Platzbecker, Uwe
A1  - Schäfer-Eckart, Kerstin
A1  - Krämer, Alwin
A1  - Berdel, Wolfgang E.
A1  - Serve, Hubert
A1  - Ehninger, Gerhard
A1  - Schuler, Ulrich
T1  - Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicin for acute myeloid leukemia in elderly patients
T2  - Annals of oncology
N2  - Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA).
Patients and methods: Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1–3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1–7) plus daunorubicin (45 mg/m2 days 3–5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone.
Results: Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33–45] versus 55% (95% CI: 49–61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513).
Conclusion: The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve curative treatment for elderly AML patients.
KW  - acute myeloid leukemia
KW  - cytarabine dose
KW  - elderly
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53569
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-535693
SN  - 1569-8041
SN  - 0923-7534
N1  - User License: Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)
VL  - 29
IS  - 4
SP  - 973
EP  - 978
PB  - Oxford Univ. Press
CY  - Oxford
ER  -