Cited by 961Acute Myeloid Leukemia ResearchRetinoids in leukemia and cellular processesHematopoietic Stem Cell Transplantation

Azacitidine Prolongs Overall Survival Compared With Conventional Care Regimens in Elderly Patients With Low Bone Marrow Blast Count Acute Myeloid Leukemia

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Fenaux, Pierre, Mufti, Ghulam J., Hellström-Lindberg, Eva, Santini, Valeria, Gattermann, Norbert, Germing, Ulrich, Sanz, Guillermo, List, Alan F. +8 more·2010·Journal of Clinical Oncology

Abstract

Purpose: In a phase III randomized trial, azacitidine significantly prolonged overall survival (OS) compared with conventional care regimens (CCRs) in patients with intermediate-2– and high-risk myelodysplastic syndromes. Approximately one third of these patients were classified as having acute myeloid leukemia (AML) under current WHO criteria. This analysis compared the effects of azacitidine versus CCR on OS in this subgroup. Patients and Methods: Patients were randomly assigned to receive subcutaneous azacitidine 75 mg/m 2 /d or CCR (best supportive care [BSC] only, low-dose cytarabine (LDAC), or intensive chemotherapy [IC]). Results: Of the 113 elderly patients (median age, 70 years) randomly assigned to receive azacitidine (n = 55) or CCR (n = 58; 47% BSC, 34% LDAC, 19% IC), 86% were considered unfit for IC. At a median follow-up of 20.1 months, median OS for azacitidine-treated patients was 24.5 months compared with 16.0 months for CCR-treated patients (hazard ratio = 0.47; 95% CI, 0.28 to 0.79; P = .005), and 2-year OS rates were 50% and 16%, respectively (P = .001). Two-year OS rates were higher with azacitidine versus CCR in patients considered unfit for IC (P = .0003). Azacitidine was associated with fewer total days in hospital (P < .0001) than CCR. Conclusion: In older adult patients with low marrow blast count (20% to 30%) WHO-defined AML, azacitidine significantly prolongs OS and significantly improves several patient morbidity measures compared with CCR.

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Crossref · 10.1200/jco.2009.23.8329

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  • The prolonged time to initial response, typically around 3 months from treatment onset, is consistent with the primary effects of low dose treatment being mediated via DNA demethylation and epigenetic reprogramming as opposed to direct cytotoxicity.

    “The prolonged time to initial response, which typically occurs around 3 months from treatment onset 125 , is consistent with the primary effects of low dose treatment being mediated via DNA demethylation and epigenetic reprogramming as opposed to direct cytotoxicity 126-128 .”

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Authors
Fenaux, P., Mufti, G. J., Hellström-Lindberg, E., Santini, V., Gattermann, N., Germing, U., Sanz, G., List, A. F., Gore, S., Seymour, J. F., Dombret, H., Backstrom, J., Zimmerman, L., McKenzie, D., Beach, C. L., & Silverman, L. R.
Affiliations
  • Karolinska University Hospital (SE)
  • From the Avicenne, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris XIII, Bobigny; Hôpital Saint-Louis, AP-HP, Université Paris 7, Paris, France; King's College Hospital, London, United Kingdom; Karolinska University Hospital (Huddinge), Stockholm, Sweden; Azienda Ospedaliera Universitaria Careggi, Florence, Italy; Universitätsklinikum Düsseldorf, Düsseldorf, Germany; Hospital Universitario La Fe, Valencia, Spain; Peter MacCallum Cancer Centre and University of Melbourne, Melbourne,...
Venue
Journal of Clinical Oncology
Published
2010-02-01
Volume
28
Issue
4
Pages
562-569
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
OpenAlex
W2157287007
Cited by
961
References
51
Citations by year
2026: 13 · 2025: 20 · 2024: 21 · 2023: 38 · 2022: 39 · 2021: 54 · 2020: 75 · 2019: 71 · 2018: 63 · 2017: 75 · 2016: 70 · 2015: 79 · 2014: 88 · 2013: 78 · 2012: 77
FWCI
38.95
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Oncology (publishedVersion)
  • PubMed (publishedVersion)
  • Florence Research (University of Florence) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
  • Amgen
  • GlaxoSmithKline
  • Celgene
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords
azacitidine, acute myeloid leukemia, elderly patients, overall survival, myelodysplastic syndrome, low-dose cytarabine, intensive chemotherapy, best supportive care, length of hospital stay
MeSH terms
Aged, Aged, 80 and over, Antimetabolites, Antineoplastic, Antineoplastic Combined Chemotherapy Protocols, Azacitidine, Blast Crisis, Bone Marrow Cells, Female, Follow-Up Studies, Humans, International Agencies, Leukocyte Count, Male, Middle Aged, Neoplasm Staging, Prognosis, Leukemia, Myeloid, Acute, Survival Rate, Treatment Outcome, Maximum Tolerated Dose

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