Response and tolerability of a 5-day azacytidine schedule in pateints with myelodysplastic syndromes

Abstract

16532 Background: Azacitidine (AZA) is a DNA methyltransferase inhibitor with activity in patients with myelodysplastic syndrome (MDS). The current approved schedule of AZA is 75 mg/m2/d for 7 days every 28 days. This schedule is inconvenient for patients and providers because of the need for weekend administration. Methods: The records of 9 patients who received AZA 100 mg/m2/d for 5 days with an anticipated 28 day cycle between 10/04 to 1/06 were reviewed to determine response, duration of response and tolerability. A minimum of two cycles were required for response evaluation (n = 8). All patients were assessed for tolerability. The International Working Group response criteria for MDS was utilized for evaluation. Results: Patients had secondary MDS (n = 4), chronic myelomonocytic leukemia (n = 2), refractory anemia (n = 2) and refractory anemia with ringed sideroblasts (n = 1). Of the 8 patients who received at least 2 cycles of therapy, 5 responded: 1 achieved partial response, 3 achieved hematologic improvement in at least one cell line and 1 remained in a stable disease state. The overall response rate was 63%. Average response duration was 6.2 months. The longest response duration was 10 months. Myelosuppression was seen in 2 of the 9 patients treated, one of whom continued treatment with growth factor support; therapy is currently on hold for the other patient. Injection site reaction was seen in 2 patients, resulting in discontinuation of treatment in one. One patient experienced severe malaise after 2 cycles and was given the standard dose for further therapy with a major hematologic improvement. Other isolated events included mouth ulcers, mild nausea and flare of erythema nodosum. Of the 5 responders, 1 later died of disease progression (after 7 cycles), 1 died of a complication of comorbidity (after 5 cycles), 1 is alive with disease progression (after 10 cycles) and 2 are continuing therapy with AZA (after 4 and 5 cycles, respectively). Conclusions: AZA 100 mg/m2/day for 5 days every 28 days seems to be tolerated as well as the 7-day treatment schedule. It also appears to have efficacy similar to the standard dose and schedule. If larger studies are confirmatory, this 5-day schedule may be more convenient for patients and providers. [Table: see text]