Randomized open-label phase II study of decitabine in patients with low- or intermediate-risk myelodysplastic syndromes.

PURPOSE: This open-label, randomized phase II trial assessed efficacy and tolerability of two low-dose regimens of subcutaneous (SC) decitabine in patients with low- or intermediate-1-risk myelodysplastic syndrome (MDS).

PATIENTS AND METHODS: Patients received decitabine 20 mg/m(2) SC per day for 3 consecutive days on days 1, 2, and 3 every 28 days (schedule A) or 20 mg/m(2) SC per day once every 7 days on days 1, 8, and 15 every 28 days (schedule B) for up to 1 year. Primary efficacy end point was overall improvement rate (OIR: complete remission [CR], partial remission [PR], marrow CR [mCR], or hematologic improvement [HI]). Secondary end points were HI, transfusion independence, cytogenetic response, overall survival (OS), and time to acute myeloid leukemia or death.

RESULTS: Efficacy and safety populations were identical: schedule A, n = 43; schedule B, n = 22. Median time from MDS diagnosis to treatment was 3.6 months; 89% had de novo MDS. The trial was terminated early on achievement of protocol-defined OIR superiority of schedule A over schedule B; OIR was 23% for schedule A (seven CRs, three HIs) and 23% for schedule B (one mCR, one PR, three HIs). No differences were observed in secondary end points. Median OS was not reached; approximately 70% of patients were alive at 500 days. Patients in schedule A (67%) and schedule B (59%) were RBC/platelet independent on study. The most frequent drug-related adverse events overall were neutropenia (28% v 36%), anemia (23% v 18%), and thrombocytopenia (16% v 32%).

CONCLUSION: In this phase II study, low-dose decitabine showed promising results in patients with low- or intermediate-1-risk MDS.