Document Detail


The role of decitabine in the treatment of myelodysplastic syndromes.
MedLine Citation:
PMID:  17163808     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Supportive care with red cell and platelet transfusions and use of growth factors has long been the standard of care for patients with myelodysplastic syndromes (MDS) ineligible for stem cell transplantation. Although these measures improve quality of life, their impact on the natural history of the disease is questionable. Recently, three new agents have been approved for the treatment of MDS. These include: 5-azacytidine, lenalidomide and, more recently, 5-aza-2 -deoxycytidine (decitabine). Decitabine is a hypomethylating agent that is incorporated into DNA and forms irreversible covalent adducts with DNA-methyltransferases. At high concentrations, this leads to cell death. At low concentrations, decitabine is considered to exert its anticancer effects by inducing DNA hypomethylation. This results in reactivation of epigenetically repressed genes, such as tumour suppressor genes and, potentially, cell differentiation. In a randomized, Phase III trial of decitabine versus best supportive care in patients with MDS, the overall response rate with decitabine was 17%, including 9% complete remissions. Patients at high risk had a statistically significant prolongation of time to acute myelogenous leukemia transformation or death. This experience has been followed by a study of low-dose decitabine using a five-times daily 1-h infusion schedule, with significant efficacy in patients with MDS observed. Ongoing studies are evaluating the activity and safety of the combination of decitabine with several histone deacetylase inhibitors and other indications. This article summarizes the experience in with decitabine in MDS.
Authors:
Ehab Atallah; Hagop Kantarjian; Guillermo Garcia-Manero
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Expert opinion on pharmacotherapy     Volume:  8     ISSN:  1744-7666     ISO Abbreviation:  Expert Opin Pharmacother     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-13     Completed Date:  2007-02-22     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  100897346     Medline TA:  Expert Opin Pharmacother     Country:  England    
Other Details:
Languages:  eng     Pagination:  65-73     Citation Subset:  IM    
Affiliation:
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Azacitidine / analogs & derivatives*,  chemistry,  pharmacology,  therapeutic use
Clinical Trials, Phase III as Topic
DNA Methylation / drug effects
Drug Therapy, Combination
Humans
Myelodysplastic Syndromes / drug therapy*,  epidemiology
Chemical
Reg. No./Substance:
320-67-2/Azacitidine; 776B62CQ27/decitabine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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