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Optimizing therapy with methylation inhibitors in myelodysplastic syndromes: dose, duration, and patient selection

Nature Clinical Practice Oncology volume 2, pages S24–S29 (2005)Cite this article

Abstract

Azacitidine (Vidaza®, Pharmion Corp., Boulder, CO, USA) and decitabine (Dacogen™, SuperGen, Inc., Dublin, CA, USA, and MGI Pharma, Inc., Bloomington, MN, USA) are DNA methyltransferase (DNMT) inhibitors that have clinical activity in patients with myelodysplastic syndromes. Mechanism-based laboratory studies suggest that clinical optimization of therapy with DNMT inhibitors needs to include optimizing intracellular drug uptake and maximizing drug exposure over time while still using lower doses to avoid cytotoxicity. Clinical studies suggest that increased dose intensity and multiple cycles of administration substantially increase response rates. Other strategies for optimizing the efficacy of DNMT inhibitor therapy also include identification of patients that are best qualified for treatment, and defining in vivo mechanisms of patient responses. In the future, combination strategies to increase gene reactivation and to take advantage of increased expression of target genes may be critical for achieving optimal results.

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Authors and Affiliations

  1. Professor and Chief of the Section of Translational Research in the Department of Leukemia at the MD Anderson Cancer Center, University of Texas, Houston, TX, USA

    Jean-Pierre Issa

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  1. Jean-Pierre Issa
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Correspondence to Jean-Pierre Issa.

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Competing interests

Prof Jean-Pierre Issa has received consulting fees, lecture fees, and research support from SuperGen Corp., MGI Pharma Inc., and Pharmion Corp.

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Issa, JP. Optimizing therapy with methylation inhibitors in myelodysplastic syndromes: dose, duration, and patient selection. Nat Rev Clin Oncol 2 (Suppl 1), S24–S29 (2005). https://doi.org/10.1038/ncponc0355

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