This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kaminskas, E. Articles by Pazdur, R. Search for Related Content PubMed PubMed Citation Articles by Kaminskas, E. Articles by Pazdur, R.

Approval Summary: Azacitidine for Treatment of Myelodysplastic Syndrome Subtypes

Authors' Affiliation: Division of Oncology Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland

Requests for reprints: Edvardas Kaminskas, Food and Drug Administration, HFD-150, 5600 Fishers Lane, Rockville, MD 20857. Phone: 301-594-5753; Fax: 301-594-0499; E-mail: edvardas.kaminskas{at}fda.hhs.gov.

Purpose: This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome.

Experimental Design: In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks.

Results: In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths.

Conclusions: On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda.gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.

Key Words: Azacitidine • Vidaza • Myelodysplastic syndrome • Refractory anemia • Acute myeloid leukemia

This article has been cited by other articles:

				R. L. Piekarz and S. E. Bates Epigenetic Modifiers: Basic Understanding and Clinical Development Clin. Cancer Res., June 15, 2009; 15(12): 3918 - 3926. [Abstract] [Full Text] [PDF]

				P. A. Link, M. R. Baer, S. R. James, D. A. Jones, and A. R. Karpf p53-Inducible Ribonucleotide Reductase (p53R2/RRM2B) Is a DNA Hypomethylation-Independent Decitabine Gene Target That Correlates with Clinical Response in Myelodysplastic Syndrome/Acute Myelogenous Leukemia Cancer Res., November 15, 2008; 68(22): 9358 - 9366. [Abstract] [Full Text] [PDF]

				D. Haase, U. Germing, J. Schanz, M. Pfeilstocker, T. Nosslinger, B. Hildebrandt, A. Kundgen, M. Lubbert, R. Kunzmann, A. A. N. Giagounidis, et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients Blood, December 15, 2007; 110(13): 4385 - 4395. [Abstract] [Full Text] [PDF]

				C. B. Yoo, S. Jeong, G. Egger, G. Liang, P. Phiasivongsa, C. Tang, S. Redkar, and P. A. Jones Delivery of 5-Aza-2'-Deoxycytidine to Cells Using Oligodeoxynucleotides Cancer Res., July 1, 2007; 67(13): 6400 - 6408. [Abstract] [Full Text] [PDF]

				H. Kantarjian, Y. Oki, G. Garcia-Manero, X. Huang, S. O'Brien, J. Cortes, S. Faderl, C. Bueso-Ramos, F. Ravandi, Z. Estrov, et al. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia Blood, January 1, 2007; 109(1): 52 - 57. [Abstract] [Full Text] [PDF]

				A. Raza, F. Z. Raza, N. Galili, H. M. Kantarjian, Y. Oki, and J.-P. Issa Low-dose decitabine and high-risk MDS Blood, December 15, 2006; 108(13): 4291 - 4292. [Full Text] [PDF]

				A. P. Mitra, R. H. Datar, and R. J. Cote Molecular Pathways in Invasive Bladder Cancer: New Insights Into Mechanisms, Progression, and Target Identification J. Clin. Oncol., December 10, 2006; 24(35): 5552 - 5564. [Abstract] [Full Text] [PDF]

				B. D. Cheson, P. L. Greenberg, J. M. Bennett, B. Lowenberg, P. W. Wijermans, S. D. Nimer, A. Pinto, M. Beran, T. M. de Witte, R. M. Stone, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia Blood, July 15, 2006; 108(2): 419 - 425. [Abstract] [Full Text] [PDF]

				S. D. Nimer Clinical Management of Myelodysplastic Syndromes With Interstitial Deletion of Chromosome 5q J. Clin. Oncol., June 1, 2006; 24(16): 2576 - 2582. [Abstract] [Full Text] [PDF]

				N. Vey, A. Bosly, A. Guerci, W. Feremans, H. Dombret, F. Dreyfus, D. Bowen, A. Burnett, M. Dennis, V. Ribrag, et al. Arsenic Trioxide in Patients With Myelodysplastic Syndromes: A Phase II Multicenter Study J. Clin. Oncol., June 1, 2006; 24(16): 2465 - 2471. [Abstract] [Full Text] [PDF]

				B. H. Lee, S. Yegnasubramanian, X. Lin, and W. G. Nelson Procainamide Is a Specific Inhibitor of DNA Methyltransferase 1 J. Biol. Chem., December 9, 2005; 280(49): 40749 - 40756. [Abstract] [Full Text] [PDF]

				L. F. Zerbini and T. A. Libermann GADD45 Deregulation in Cancer: Frequently Methylated Tumor Suppressors and Potential Therapeutic Targets Clin. Cancer Res., September 15, 2005; 11(18): 6409 - 6413. [Full Text] [PDF]