Abstract

PURPOSE Efficacy and toxicity profile of orally administered clofarabine were evaluated in patients with higher-risk myelodysplastic syndrome (MDS). PATIENTS AND METHODS Thirty-two patients were treated, of whom 22 had intermediate-2 or high-risk disease (International Prognostic Scoring System). Median age was 70 years (range, 53 to 86), nine patients had secondary MDS, and 20 patients experienced prior therapy failure with hypomethylating agents. Three doses of clofarabine were evaluated: 40 mg/m(2), 30 mg/m(2), and 20 mg/m(2) daily for 5 days. Courses were repeated every 4 to 8 weeks. Results Eight patients (25%) achieved complete remission (CR), three had (9%) hematologic improvement (HI), and three had (9%) clinical benefit (CB; overall response rate, 43%). Responses in patients who experience treatment failure with hypomethylating agents included CR in two (10%), HI in two (10%), and CB in two patients (10%). No patients died within 6 weeks of induction. Renal failure occurred in four patients in the context of myelosuppresssion-associated infectious complications. Common adverse events were gastrointestinal and hepatic. Myelosuppression was common, but prolonged myelosuppression (> 42 days) was rare. The toxicity profile was better with lower doses of clofarabine, whereas response rates did not differ significantly. CONCLUSION Oral clofarabine has achieved a response rate of 43% in patients with higher-risk MDS. The optimal dose and schedule and the appropriate patient population for such therapy remain to be further defined.