Low-dose 5-aza-2 '-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: A multicenter phase II study in elderly patients

Purpose: 5-Aza-2'-deoxycytidine (decitabine; DAC) is a DNA hypomethylating agent that has shown a 50% response rate in a small phase It study in elder ly patients with high-risk myelodysplastic syndrome. We performed a second, multicenter phase II study in a larger group of patients ta confirm our fi ndings and to study the toxicity of DAC. Patients and Methods: Between June 1996 and September 1997, 66 patients (me dian age, 68 years) from seven centers received PAC 45 mg/m(2)/d for 3 days every 6 weeks. For patients in whom a complete response (CR) was reached a fter two courses, two further cycles were administered as consolidation the rapy, In case of a stable disease situation, improvement, or a partial resp onse (PR), ct maximum of six cycles was administered, The primary end point s were response rate and toxicity. The secondary end points were response d uration, survival from the start of therapy, and overall survival, Results: The observed overall response rate was 49%, with a 64% response ra te in the patients with an International Prognostic Scoring System (IPSS) h igh-risk score. The actuarial median response duration was 31 weeks, with a response duration of 39 weeks and 36 weeks for patients who reached a PR o r CR, respectively. The actuarial median survival time from the time of dia gnosis was 22 months and from the start of therapy was 15 months. For the I PSS high risk group, the median survival rime was 14 months. the median pro gression-free survival time was 25 weeks. Myelosuppression was rather commo n, and the treatment-related mortality rate was 7% and was primarily associ ated with pancytopenia and infection. Significant responses were observed w ith regard to megakaryopoiesis, with increases in platelet counts having al ready occurred after one cycle of DAC therapy in the majority of the respon ding patients. Conclusion: We were able to confirm our previous observation that DAC thera py was effective in half of the studied patients with high-risk myelodyspla stic syndrome and is especially active in the patients with the worst progn oses. Myelosuppression was the only major adverse effect observed. J Clin O ncol 18:956-962. (C) 2000 by American Society of Clinical Oncology.