Therapy with azanucleosides for myelodysplastic syndromes

The use of azanucleosides has altered the treatment paradigm of myelodysplastic syndromes. Recently, treatment with 5-azacitidine was demonstrated to prolong survival in patients with myelodysplastic syndromes for the first time. This Review discusses the potential of these forms of treatment as monotherapy and in combination, and assesses the most recent clinical data. Azanucleosides constitute the core therapy in the management of myelodysplastic syndromes (MDS), and have altered the treatment paradigm of MDS, previously dominated by supportive care strategies. DNA methylation regulates gene transcription in MDS, and it is hypothesized that azanucleoside therapy induces DNA hypomethylation and re-expression of aberrantly silenced genes in patients with these disorders. A series of clinical trials conducted over the past 5 years has demonstrated the activity of these therapies. Two agents, 5-azacitidine and decitabine, have been approved by the FDA for treatment of MDS. Recently, 5-azacitidine therapy has been shown, for the first time, to prolong survival in patients with MDS. Because the targeting of biologic pathways in MDS is best accomplished by combining agents with complementary mechanisms of action, combinations of azanucleosides with other drugs are being investigated. In this article, we critically appraise the most relevant clinical data reported on the use of azanucleosides for the treatment of patients with MDS.