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BMC Hematol. 2018 Feb 1;18:4. doi: 10.1186/s12878-018-0095-2. eCollection 2018.

More is less, less is more, or does it really matter? The curious case of impact of azacitidine administration schedules on outcomes in patients with myelodysplastic syndromes.

Author information

1
1Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT USA.
2
3Section of Hematology, Department of Internal Medicine, Yale University, 333 Cedar Street, PO Box 208028, New Haven, CT 06520-8028 USA.
3
2Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University, New Haven, CT USA.

Abstract

Myelodysplastic syndromes (MDS) encompass a diverse group of hematologic disorders characterized by ineffective and malignant hematopoiesis, peripheral cytopenias and significantly increased risk of progression to acute myeloid leukemia (AML). The hypomethylating agents (HMA) azacitidine and decitabine induce meaningful clinical responses in a significant subset of patients with MDS. Though never compared directly with decitabine, only azacitidine has improved overall survival (OS) compared to conventional care in a randomized trial in patients with higher-risk MDS. The azacitidine regimen used in this pivotal trial AZA-001 included administration at 75 mg/m2/day for 7 consecutive days in 28-day cycles (7-0 regimen). Given the logistical difficulties of weekend administration in the 7-0 regimen, as well as in efforts to improve response rates, alternative dosing schedules have been used. In a typical 28-day cycle, administration schedules of 3, 5, 10, and (with the oral version of azacitidine) 14 and 21 days have been used in clinical trials. Most trials that evaluated alternative administration schedules of azacitidine did so in lower-risk MDS and did not directly compare to the 7-0 schedule. Given the lack of randomized prospective studies comparing the 7-0 schedule to the other regimens of azacitidine in MDS, Shapiro et al. conducted a systematic review in an attempt to answer this question. Here we place the findings of this important work in clinical context and review the current knowledge and unresolved issues regarding the impact of administration schedules of azacitidine on outcomes of patients with both lower-risk and higher-risk MDS.

KEYWORDS:

Azacitidine; Decitabine; HMAs; Hypomethylating agents; MDS; Myelodysplastic syndrome

Conflict of interest statement

Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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