Concise Drug Review: Azacitidine and Decitabine

INTRODUCTION The hypomethylating agents azacitidine and decitabine (5-aza-2'-deoxycytidine) are currently approved for the treatment of several specific forms of myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML), as depicted in Table 1. The only potentially curative therapy for patients with higher-risk MDS (International Prognostic Scoring System intermediate-2 risk and high risk) is an allogeneic stem cell transplantation (allo-SCT). However, for the majority of patients, allo-SCT is not an option because of advanced age and/or comorbidities. In addition, the results obtained with intensive chemotherapy (when feasible) are often disappointing. For patients with MDS, the probability of complete remission after intensive chemotherapy is generally lower and the remission duration shorter than for patients with primary AML [1]. Therefore, the introduction of the hypomethylating agents has been a major advancement in the treatment of patients with higher-risk MDS who are ineligible for allo-SCT. Table 2 summarizes the key pharmacologic features of these two agents. The pivotal phase III trial investigating azacitidine treatment in patients with higher-risk MDS demonstrated a significant improvement of overall survival compared to supportive care or low-dose cytarabine. However, when compared to intensive chemotherapy, there was no significant difference in overall survival [2]. In the absence of undisputed, comparative data, it remains uncertain whether hypomethylating agents should always be preferred over intensive chemotherapy [3]. In contrast to azacitidine, decitabine showed no beneficial effect on overall survival or time to AML in patients with MDS, even though the response percentages obtained with azacitidine and decitabine were almost the same [2, 4, 5]. The fact that a survival benefit in patients with MDS was found for azacitidine and not for decitabine does not necessarily indicate a discrepant pharmacology. The difference may also be explained by the differences in study design in particular the inclusion criteria, the number of treatment cycles, and whether or not postprogression treatment was allowed.