Journal of Clinical Oncology, Vol 18, Issue 5
(March), 2000: 956
© 2000 American Society for Clinical Oncology
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
By P. Wijermans,
M. Lübbert,
G. Verhoef,
A. Bosly,
C. Ravoet,
M. Andre,
A. Ferrant
From the Department of Haematology, Leyenburg Hospital, The Hague, the Netherlands; University Hospital, Albert-Ludwigs University, Freiburg, Germany; University Hospital Gasthuisberg, Leuven; Mont-Godinne UCL University Hospital, Yvoir; Hospital de Jolimont, Haine Saint Paul; and Hospital Notre-Dame Charleroi and Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Address reprint requests to P.W. Wijermans, MD, Department of Haematology, Leyenburg Hospital, Leyweg 275, 2545 CH The Hague, the Netherlands; email hematley{at}worldonline.nl
PURPOSE: 5-Aza-2'-deoxycytidine (decitabine; DAC) is a DNA hypomethylating agent that has shown a 50% response rate in a small phase II study in elderly patients with high-risk myelodysplastic syndrome. We performed a second, multicenter phase II study in a larger group of patients to confirm our findings and to study the toxicity of DAC.
PATIENTS AND METHODS: Between June 1996 and September 1997, 66 patients (median age, 68 years) from seven centers received DAC 45 mg/m2/d for 3 days every 6 weeks. For patients in whom a complete response (CR) was reached after two courses, two further cycles were administered as consolidation therapy. In case of a stable disease situation, improvement, or a partial response (PR), a maximum of six cycles was administered. The primary end points were response rate and toxicity. The secondary end points were response duration, survival from the start of therapy, and overall survival.
RESULTS: The observed overall response rate was 49%, with a 64% response rate in the patients with an International Prognostic Scoring System (IPSS) high-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 or CR, respectively. The actuarial median survival time from the time of diagnosis was 22 months and from the start of therapy was 15 months. For the IPSS high-risk group, the median survival time was 14 months. The median progression-free survival time was 25 weeks. Myelosuppression was rather common, and the treatment-related mortality rate was 7% and was primarily associated with pancytopenia and infection. Significant responses were observed with regard to megakaryopoiesis, with increases in platelet counts having already occurred after one cycle of DAC therapy in the majority of the responding patients.
CONCLUSION: We were able to confirm our previous observation that DAC therapy was effective in half of the studied patients with high-risk myelodysplastic syndrome and is especially active in the patients with the worst prognoses. Myelosuppression was the only major adverse effect observed.
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