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Further Analysis of Trials With Azacitidine in Patients With Myelodysplastic Syndrome: Studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B

Lewis R. Silverman, David R. McKenzie, Bercedis L. Peterson, James F. Holland, Jay T. Backstrom, C.L. Beach, Richard A. Larson

From the Mount Sinai School of Medicine, New York, NY; Pharmion Corporation, Overland Park, KS; Cancer and Leukemia Group B Statistical Center and Duke University, Durham, NC; and the University of Chicago, Chicago, IL

Address reprint requests to Lewis R. Silverman, MD, Division of Hematology/Oncology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1129, New York, NY 10029; e-mail: lewis.silverman{at}mssm.edu

PURPOSE: Within the last two decades, a new understanding of the biology of myelodysplastic syndrome (MDS) has developed. With this understanding, new classification systems, such as the WHO diagnostic criteria, and the International Prognostic Scoring System and response criteria guidelines reported by the International Working Group (IWG) have been developed. We report the combined results of three previously reported clinical trials (n = 309) with azacitidine using the WHO classification system for MDS and acute myeloid leukemia (AML) and IWG criteria for response.

PATIENTS AND METHODS: Data from three sequential Cancer and Leukemia Group B trials with azacitidine were recollected and reanalyzed as part of the New Drug Application process. The trials were conducted with either intravenous or subcutaneous azacitidine (75 mg/m²/d for 7 days every 28 days).

RESULTS: Complete remissions were seen in 10% to 17% of azacitidine-treated patients; partial remissions were rare; 23% to 36% of patients had hematologic improvement (HI). The median number of cycles to first response was three, and 90% of responses were seen by cycle 6. Using current WHO criteria, 103 patients had AML at baseline; 35% to 48% had HI or better responses. The median survival time for the 27 AML patients randomly assigned to azacitidine was 19.3 months compared with 12.9 months for the 25 patients assigned to observation. Furthermore, azacitidine did not increase the rate of infection or bleeding above the rate caused by underlying disease.

CONCLUSION: Azacitidine provides important clinical benefits for patients with high-risk MDS.

Supported by federal grants from the US Food and Drug Administration, by National Cancer Institute (NCI) Grant No. CA31946 to the Cancer and Leukemia Group B, and by NCI Grants No. CA04457, CA33601, and CA41287. The subsequent recollection and further analyses were sponsored by Pharmion Corporation.

The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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