Retrospective Comparison of Azacitidine and Decitabine in the Treatment of Myleodysplastic Syndrome,

Two DNA methyltransferase inhibitors, azacitidine and decitabine, are currently approved for the treatment of myleodysplastic syndrome (MDS) according to the results of several Phase II and III trials, which have demonstrated the efficacy of the agents. Despite widespread clinical use of DNA methyltransferase inhibitors, one of important practical issues is which drug should be chosen. In this retrospective study, we tried to compare azacitidine and decitabine for the treatment of MDS in regards to treatment response, toxicities, and survival. Methods: Between September 2006 and October 2010, a total of 149 patients were treated with either azacitidine (n=75) or decitabine (n=74) for MDS defined by the WHO classification and chronic myelomonocytic leukemia (CMML) in 3 Korean institutes; all are included in this analysis. Azacitidine 75 mg/m²/day was administered as a subcutaneous injection for 7 consecutive days and decitabine 20 mg/m²/day as a 1-hour intravenous infusion for 5 consecutive days. Both agents were repeated every 4 weeks. Treatment response was evaluated using modified International Working Group response criteria. Results: Median age of the patients, 100 males and 49 females, was 60 years (range, 23–83). WHO subtype at the time of decitabine treatment was RA in 18, RARS in 2, RCMD in 28, RCRS in 5, RAEB-1 in 46, RAEB-2 in 39, unclassified in 2, and CMML in 9. IPSS risk category was low/intermediate-1 in 72 and intermediate-2/high in 72. Median number of courses delivered to each patient was 5 (range, 1–31) for azacitidine and 4 (range, 1–24) for decitabine (P=0.033). Hematologic responses (CR/PR/mCR) were induced in 9 patients (12.0%) with azacitidine and in 22 (29.7%) with decitabine (P=0.008). The rates of overall response (CR/PR/mCR/HI) was not significantly different between azacitidine (52.0%) and decitabine (63.5%) (P=0.155). Median number of treatment courses to achieve any response was 2 (range, 1–6) for azacitidine and 1 (range, 1–5) for decitabine (P=0.269). Adverse events were evaluated for the first 6 courses for all patients, for a total of 584 courses. Major adverse events were cytopenia and cytopenia-related infection. Grade 3 or higher neutropenia was more frequent with decitabine (79.6%) than with azacitidine (72.2%) (P=0.040), but incidence of febrile episode requiring intravenous antibiotics was similar (12.4% with decitabine vs. 15.4% with azacitidine, P=0.298). Grade 3 or higher non-hematologic toxicities were infrequent and reversible with both agents. Median follow-up duration of surviving patients was 46.9 months (range, 11.8–55.5) for azacitidine and 22.7 months (range 3.3–33.3) for decitabine. Probabilities of overall survival (OS) at 2 years were 43.5% for azacitidine, and 55.5% for decitabine. The difference of OS in favor of decitabine over azacitidine was significant after adjustment for other variables (HR, 0.539; 95% CI, 0.325–0.895; P=0.017). Subgroup analysis showed that the survival superiority of decitabine over azacitidine was evident principally in patients with IPSS low/intermediate-1 (HR, 0.131; P=0.006), MDS duration of 1 year or less (HR, 0.534; P=0.022), or ECOG performance scale of 0–1 (HR, 0.589; P=0.060). In contrast, a tendency was noted for survival superiority of azacitidine over decitabine in patients with MDS duration over 1 year (HR, 2.107; P=0.235) or ECOG scale of 2–3 (HR, 2.492; P=0.074). Conclusions: Although both azacitidine and decitabine were effective in the treatment of patients with MDS, there were some differences between two agents in regards to response patterns, toxicities, and type of subgroups that showed more beneficial effects with the hypomethylating agent.

No relevant conflicts of interest to declare.