The role of decitabine in the treatment of myelodysplastic syndromes.
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.
Atallah
Ehab
E
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Kantarjian
Hagop
H
Garcia-Manero
Guillermo
G
D001374:Azacitidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D004359:Drug Therapy, Combination; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000453:epidemiology
D000077209:Decitabine; D001374:Azacitidine