Methylation inhibitor therapy in the treatment of myelodysplastic syndrome

Lewis R. Silverman, Ghulam J. Mufti

Research output: Contribution to journalReview articlepeer-review

63 Scopus citations


The class of DNA methyltransferase inhibitors is represented by azacitidine and decitabine. Azacitidine is approved for the treatment of patients in both low- and high-risk subtypes of myelodysplastic syndrome (MDS), and decitabine is currently under review by the FDA. Azacitidine phase III trial data, based upon the Cancer and Leukemia Group B (CALGB) study 9221, showed durable clinical and symptomatic improvement in bone marrow function, a reduction in the risk of leukemic transformation, and significant improvements in the quality of life of patients treated with azacitidine compared with supportive care alone. This study also provided data suggestive of improvement in survival in MDS patients. The experience with decitabine comprises a number of phase I/II studies and a phase III trial yet to be published. While there is a strong base of experience supporting the efficacy of DNA methyltransferase inhibitors in the treatment of MDS, a number of practical issues need to be explored further. These include the optimization of the timing and duration of treatment, and the prediction of response to therapy. Along with current experience, future studies will lead to the development of treatment algorithms, strategies for selecting patients (e.g. according to age, risk, classification, and cytogenetic profile), and the combination strategies, particularly with histone deacetylase inhibitors, in the management of MDS.

Original languageEnglish
Pages (from-to)S12-S23
JournalNature Clinical Practice Oncology
Issue numberSUPPL. 1
StatePublished - Dec 2005


  • Azacitidine
  • Clinical trials
  • Decitabine
  • Hypomethylation
  • Myelodysplastic syndrome


Dive into the research topics of 'Methylation inhibitor therapy in the treatment of myelodysplastic syndrome'. Together they form a unique fingerprint.

Cite this