Clinical experience with decitabine in North American patients with myelodysplastic syndrome

Karen W L Yee, Elias Jabbour, Hagop M. Kantarjian, Francis J. Giles*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Recent evidence demonstrates that epigenetic silencing of genes is associated with myelodysplasia and that a worse prognosis may be correlated with hypermethylation of certain genes, such as the cyclin-dependent kinase inhibitor p15. 5-Aza-2′-deoxycytidine (decitabine, DAC) is a nucleoside analog, which, at low doses, acts as a hypomethylating agent and is fivefold to tenfold more active than 5-azacytidine (azacitidine, Vidaza) - currently the only approved drug for treatment of myelodysplastic syndrome (MDS). Clinical studies have demonstrated that decitabine has activity in patients with MDS. Preliminary results of a phase III multicenter North American trial comparing low-dose decitabine to supportive care verified that therapy with decitabine resulted in higher response rates, improved quality of life, and prolonged time to leukemic transformation and/or death. However, further elucidation of its mechanism of action is required, as clinical response to decitabine does not correlate with demethylation of the p15 gene promoter or the repetitive DNA element LINE. Decitabine appears to upregulate both hypermethylated and nonmethylated genes. Ongoing studies aim to determine the optimal dose, schedule, and route of administration of decitabine, and to evaluate whether efficacy can be improved by using it in combination with other agents, such as histone deacetylase inhibitors.

Original languageEnglish (US)
Pages (from-to)18-24
Number of pages7
JournalAnnals of Hematology, Supplement
Volume84
Issue number13
DOIs
StatePublished - Dec 2005

Keywords

  • Clinical trials
  • Decitabine
  • Histone deacetylase inhibitor
  • Hypomethylation
  • MDS
  • Myelodysplastic syndrome
  • Valproic acid

ASJC Scopus subject areas

  • Hematology

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