A comparison of therapeutic dosages of decitabine in treating myelodysplastic syndrome: a meta-analysis

Abstract

Decitabine is used to treat myelodysplastic syndrome (MDS). This meta-analysis evaluated the efficacy and safety of different dosing regimens of decitabine in treating intermediate and/or high-risk MDS. Medline, Cochrane, EMBASE, and Google Scholar databases were searched up to October 23, 2015. Randomized controlled trials, prospective, cohort, and case series studies were included. Fifteen studies were included with a total of 1378 patients. The decitabine 100 mg/m/course dosing regimen had a greater overall response rate than the 60-75 mg/m/course (51 vs. 25%; P = 0.003). It also had higher complete response rate compared with the 135 mg/m/course regimen (24.2 vs.13.7%; P = 0.016). The three dosing regimens were similar with respect to bone marrow complete response and partial response and hematologic improvement (P values > 0.05). Decitabine 135 mg/m/course regimen had similar hematologic improvement as best supportive care (P = 0.066). The incidence of neutropenia, thrombocytopenia, infections, and anemia was similar across treatment groups (range, 31 to 38%; P values ≥ 0.899). The 100 mg/m/course decitabine regimen showed benefit with respect to overall response rate compared with the 60-75 mg/m/course regimen, as well as greater improvement in complete response rate compared with the 135 mg/m/course regimen. All three dosing regimens had similar frequency of adverse events.

High-dose regimens of hypomethylating agents promote transfusion independence in IPSS lower-risk myelodysplastic syndromes: a meta-analysis of prospective studies

“…The meta-analysis revealed that the therapeutic regimen influences treatment response rate. DAC 15 mg/m 2 /8 h for 3 days every 42 days was inferior to the other regimens, which is consistent with a previous report demonstrating that it was less effective than DAC 20×5 every 28 days for all-risk MDS [ 21 ]. However, among 28-day regimens, AZA 75×7 and DAC 20×5 had the highest response rates, although a statistical analysis was not possible because of the high heterogeneity, or did not show statistically significant differences because of the limited data.…”

“…The patients in our study were mainly ESA/EPO-refractory and transfusion-dependent, and could have a very poor outcome if left untreated. Based on the clinical characteristics of our cohort, HMAs could benefit relatively high-risk patients (int-1–risk) within the LR-MDS group, at least for the short term, as suggested by other studies [ 20 , 21 ]. However, because of the paucity of studies and lack of detailed information, we were unable to determine which WHO/FAB classifications would benefit most from HMAs TI rate is an important parameter for LR-MDS patients as it reflects patients’ quality of life and risk of leukemic transformation and mortality.…”

Incidence and risk of hematologic toxicities with hypomethylating agents in the treatment of myelodysplastic syndromes and acute myeloid leukopenia

“…A meta-analysis suggested that decitabine at 100 mg/m 2 /course dosing regimen had a greater clinical benefit in treating MDS than decitabine at 60 to 75 mg/m 2 /course and 135 mg/m 2 /course regimens. [ 56 ]…”

Infection control in patients with myelodysplastic syndromes who are candidates for active treatment: Expert panel consensus-based recommendations

“…Dosage: a higher risk of infectious complications was observed in patients treated with azacitidine 75 mg/m 2 for 7 days, than in those receiving 5 days of therapy [39,40]. This association was not observed in other experiences [23,26] The rate of infections in decitabine-treated patients did not decrease when reducing the decitabine dose [46]. Cycles: the rate of infectious events was higher in the first 3 azacitidine cycles and tended to decline with sequential cycles [7,23,25,26,41,42].…”

“…Infection-related deaths occurred only in Gram-negative events (13%); infection-related complications occurred during any cycle of therapy, and the incidence did not decrease during later cycles [22]. A recent meta-analysis has indicated that the rate of infections in decitabine-treated patients did not decrease when reducing the decitabine dose [46].…”