5-azacitidine (5-AZA) is the first hypomethylating agent synthetized and the cornerstone treatment for high-risk myelodysplastic neoplasms (MDS) and chronic myelomonocytic leukaemia (CMML). Although the validated schedule is 75 mg/m2 for 7 days (7-0-0), alternative schedules have been studied in terms of efficacy, complications and survival. The 7-0-0 shows an overall survival (OS) between 21 and 25 months in prospective and 16.5-27 months in retrospective studies and complete response (CR) rates between 7% and 18%. Alternative schedules, mostly 5-day (5-0-0) or 7-day with weekend pause (5-2-2) at 75 mg/m2, perform equally in terms of OS and CR with the 7-0-0, with a slight superiority for the 5-2-2, although direct comparisons are rare and almost always non-significant. Similarly, transfusion independence, time to leukaemia transformation and toxicities did not differ significantly across studies. For more intensive schedules, using 100 mg/m2 for 5 days, literature is limited, but response rates, survival and safety seem to be comparable to the 75 mg/m2 dose. In CMML, 5-AZA monotherapy yields satisfying overall response rates of 40% or more, with myelodysplastic subtype responding better than myeloproliferative. In all, alternative 5-AZA schedules seem non-inferior in terms of efficacy and toxicities and can be used as an alternative according to local protocols and patient choice.
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