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Published Online, 6 September 2005, www.theannals.com, DOI 10.1345/aph.1E612.
 The Annals of Pharmacotherapy: Vol. 39, No. 10, pp. 1700-1708. DOI 10.1345/aph.1E612
© 2005 Harvey Whitney Books Company.
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NEW DRUG DEVELOPMENTS

5-Azacytidine and Decitabine Monotherapies of Myelodysplastic Disorders

Jim R Kuykendall, PhD PharmD1

1 Assistant Professor of Medicinal Chemistry, Department of Biomedical and Pharmaceutical Sciences, Raabe College of Pharmacy, Ohio Northern University, 525 S. Main St., Ada, OH 45810-1599, fax 419/772-1917, j-kuykendall{at}onu.edu

Reprints: Dr. Kuykendall

OBJECTIVE: To review and differentiate the pharmacology, toxicology, pharmacokinetics, and results of major clinical trials of 5-azacytidine (5-AzaC) and 5-aza-2'-deoxycytidine (decitabine) therapy of myelodysplastic disorders.

DATA SOURCES: A PubMed/MEDLINE search was conducted (1966-October 2004) using the following terms: DNA methylation, myelodysplastic disorders, 5-azacytidine, and 5-aza-2'-deoxycytidine (decitabine). Additional data sources included bibliographies from identified articles and manufacturer information.

STUDY SELECTION AND DATA EXTRACTION: Clinical trials for the treatment of various malignancies by hypomethylating agents were selected from data sources. All published, major clinical trials evaluating 5-AzaC or decitabine in myelodysplastic disorders and transformed myeloid leukemia treatment were included.

DATA SYNTHESIS: Myelodysplastic disorders are a group of bone marrow stem cell hyperplasias and dysplasias that result in ineffective hematopoiesis. Myelodysplastic disorders and transformed leukemia have poor prognosis and minimal response to chemotherapy. DNA hypomethylating agents have been shown to improve overall response rates (increased neutrophil, leukocyte, and platelet counts), time to leukemic progression, and quality of life compared with supportive therapy. The incidence of the most common adverse effects (nausea, vomiting, myelosuppression) can be reduced by low-dose, continuous, or extended-interval infusion.

CONCLUSIONS: Since appropriate dosing schedules of decitabine are being investigated, comparison of the clinical effectiveness of 5-AzaC and decitabine would be premature at this time. DNA hypomethylating agents show promise as monotherapies of myelodysplastic disorders and transformed leukemia and may be useful as a component of combination chemotherapy of various malignancies.

Key Words: 5-azacytidine, 5-aza-2'-deoxycytidine, decitabine, acute myelogenous leukemia, myelodysplastic syndrome

Published Online, September 6, 2005. www.theannals.com, DOI 10.1345/aph.1E612

THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT
ACPE UNIVERSAL PROGRAM NUMBER: 407-000-05-029-H01




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