5-azacitidine prolongs overall survival in patients with myelodysplastic syndrome--a systematic review and meta-analysis.
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 time-to-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.
Institute of Hematology, Davidoff Cancer Center Beilinson Hospital, Rabin Medical Center, Petah-Tikva 49100, Israel. /ronitg@clalit.org.il
Ronit
R
Gurion
Liat
L
Vidal
Anat
A
Gafter-Gvili
Yulia
Y
Belnik
Moshe
M
Yeshurun
Pia
P
Raanani
Ofer
O
Shpilberg
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000077209:Decitabine; D006801:Humans; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine