5-azacitidine prolongs overall survival in patients with myelodysplastic syndrome - a systematic review and meta-analysis

Abstract

Hypomethylating agents have recently been shown to improve the outcome of patients with myelodysplastic syndrome. A meta-analysis and systematic review was carried out of randomized controlled trials comparing treatment with hypomethylating agents to conventional care, i.e., best supportive care or chemotherapy, in patients with myelodysplastic syndrome. The outcomes assessed were overall survival, time to transformation or death, overall response rate and toxicity. Hazard ratios with 95% confidence intervals were estimated and pooled for timeto-event data. For dichotomous data, relative risks were estimated and pooled. Four trials including 952 patients examined the effect of 5-azacitidine and decitabine. Treatment with hypomethylating agents significantly improved overall survival (hazard ratio 0.72, 95% confidence interval 0.60-0.85, three trials) and time to transformation or death (hazard ratio 0.69, 95% confidence interval 0.58-0.82, four trials). In a subgroup analysis per type of drug, these benefits could be shown for 5-azacitidine but not for decitabine. Both agents favorably influenced response rates. A higher rate of grade 3/4 adverse events was observed with their use. Since 5-azacitidine prolongs overall survival and time to transformation or death it should be highly considered in the treatment of patients with high-risk myelodysplastic syndrome. Further studies are needed to establish the exact role of decitabine compared to 5-azacitidine in these patients.Key words: myelodysplastic syndrome, hypomethylating agents, 5-azacitidine, decitabine. Raanani P, survival in patients with myelodysplastic syndrome -a systematic review and meta-analysis. Haematologica. 2010; 95:303-310.

Anti-leukemia activity of chaetocin via death receptor-dependent apoptosis and dual modulation of the histone methyl-transferase SUV39H1

“…10 Several drugs able to alter the epigenetic status of a cell have shown promising results for cancer treatment and DNA methyl-transferase inhibitors have been approved by the Food and Drug Administration and European Medicines Agency for the treatment of myelodysplastic syndromes. 11,12 Moreover, several histonedeacetylase inhibitors (HDACi) exhibit significant anti-tumor activity and acceptable toxicity profiles in in vitro, ex vivo and in vivo models, and are now approved or in clinical trials in monotherapy or in combination with others drugs. 13 HDACi induces TNF-related apoptosis-induced ligand-dependent cell death, 14,15 thereby exerting tumor-selective death in myeloid leukemias.…”

Signatures of DNA target selectivity by ETS transcription factors

“…The exact same site in passively de-methylated genome, therefore, presents a heterogeneous substrate for ETS paralogs (and probably other DNA-binding proteins) depending on the stage in the cell cycle or exogenous treatment with DNMT1 inhibitors ("hypomethylating agents" such as azacitidine and decitabine). Interest in this area is heightened by the advent of hypomethylating agents as clinical drugs in hematologic cancers, such as azacitidine in myelodysplastic syndrome 70 and a growing list of other malignancies.…”

Epigenetics in Cancer: The Myelodysplastic Syndrome as a Model to Study Epigenetic Alterations as Diagnostic and Prognostic Biomarkers

“…The decitabine and azacytidine are approved for treatment of patients with int-2 and high-risk MDS. Demethylating agents seem to be the best choice for elderly patients with MDS, even in case of high risk cytogenetic changes in karyotype, like monosomy 7 (Gurion et al, 2010;Szmigielska-Kaplon & Robak, 2011).…”