Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicin for acute myeloid leukemia in elderly patients

  • 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.

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Author:Christoph Röllig, Michael Kramer, Maria Gabrecht, Mathias Hänel, Regina Herbst, Ulrich Kaiser, Norbert SchmitzGND, Johannes Kullmer, Sebastian Fetscher, Hartmut Link, Luisa Mantovani Löffler, Ulrich Krümpelmann, Thomas Neuhaus, Frank Heits, Hermann EinseleORCiDGND, Barbara Ritter, Martin Bornhäuser, Johannes Schetelig, Carsten Thiede, Brigitte Mohr, Markus Schaich, Uwe PlatzbeckerORCiDGND, Kerstin Schäfer-Eckart, Alwin KrämerORCiDGND, Wolfgang E. BerdelORCiDGND, Hubert ServeORCiDGND, Gerhard EhningerGND, Ulrich Schuler
Pubmed Id:
Parent Title (English):Annals of oncology
Publisher:Oxford Univ. Press
Place of publication:Oxford
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/01/30
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:Study Alliance Leukemia (SAL)
Release Date:2020/05/20
Tag:acute myeloid leukemia; cytarabine dose; elderly
Page Number:6
First Page:973
Last Page:978
User License: Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0