Low-Dose Decitabine Versus Best Supportive Care in Elderly Patients With Intermediate-or High-Risk Myelodysplastic Syndrome (MDS) Ineligible for Intensive Chemotherapy: Final Results of the Randomized Phase III Study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group
Low-Dose Decitabine Versus Best Supportive Care in Elderly Patients With Intermediate-or High-Risk Myelodysplastic Syndrome (MDS) Ineligible for Intensive Chemotherapy: Final Results of the Randomized Phase III Study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group
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DOI：
10.1200/jco.2010.30.9245
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发表时间：
2011-05-20
影响因子：
45.3
通讯作者：
Wijermans, Pierre W.
中科院分区：
文献类型：
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作者：
Luebbert, Michael;Suciu, Stefan;Wijermans, Pierre W.
目的比较小剂量地西他滨与最佳支持治疗(BSC)对年龄在60岁或以上且不适合接受强化化疗的高危骨髓增生异常综合征(MDS)患者的疗效。患者与方法纳入233例患者(中位年龄70岁，范围60~90岁)，53%的患者具有低危细胞遗传学，随机分配的MDS病程中位数为3个月。主要终点为总生存期(OS)。地西他滨(15 mg/m(2))静脉滴注，每天3次，持续4小时以上，疗程6周。结果与BSC相比，地西他滨治疗后OS延长无统计学意义(中位数OS分别为10.1个月和8.5个月；风险比[HR]为0.88；95%CI为0.66~1.17；双侧对数等级P=0.38)。地西他滨与BSC相比，无进展生存期(PFS)显著延长(中位数PFS，6.6vs3.0个月；95%CI，0.52~0.88；P=.004；AMLFS中位数，8.8v6.1个月；HR，0.85；95%CI，0.64~1.12；P=.24)。1年后AML转化率显著降低(P=0.036)(由BSC组的33%降至地西他滨组的22%)。多因素分析显示MDS病程短的患者预后较差。完全缓解(13%v0%)，部分缓解(6%v0%)，血液学改善(15%v2%)，病情稳定(14%vs22%)，进展(29%vs68%)，发育不良(14%v0%)，不可评价(8%v8%)。服用地他滨的患者有25%出现3-4级发热性中性粒细胞减少，而服用BSC的患者出现3-4级感染的比例为7%；服用地他滨和BSC的患者发生3-4级感染的比例分别为57%和52%。地西他滨治疗与患者报告的生活质量(QOL)参数的改善有关。结论地西他滨在高危MDS的老年患者中是有效的，导致OS和AMLFS的改善(无意义)，PFS和AML的转化(有意义)，以及生活质量的改善。短MDS病程是一个独立的不良预后因素。
PurposeTo compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy.Patients and MethodsTwo-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years) were enrolled; 53% had poor-risk cytogenetics, and the median MDS duration at random assignment was 3 months. Primary end point was overall survival (OS). Decitabine (15 mg/m(2)) was given intravenously over 4 hours three times a day for 3 days in 6-week cycles.ResultsOS prolongation with decitabine versus BSC was not statistically significant (median OS, 10.1 v 8.5 months, respectively; hazard ratio [HR], 0.88; 95% CI, 0.66 to 1.17; two-sided, log-rank P = .38). Progression-free survival (PFS), but not acute myeloid leukemia (AML) -free survival (AMLFS), was significantly prolonged with decitabine versus BSC (median PFS, 6.6 v 3.0 months, respectively; HR, 0.68; 95% CI, 0.52 to 0.88; P = .004; median AMLFS, 8.8 v 6.1 months, respectively; HR, 0.85; 95% CI, 0.64 to 1.12; P = .24). AML transformation was significantly (P = .036) reduced at 1 year (from 33% with BSC to 22% with decitabine). Multivariate analyses indicated that patients with short MDS duration had worse outcomes. Best responses with decitabine versus BSC, respectively, were as follows: complete response (13% v 0%), partial response (6% v 0%), hematologic improvement (15% v 2%), stable disease (14% v 22%), progressive disease (29% v 68%), hypoplasia (14% v 0%), and inevaluable (8% v 8%). Grade 3 to 4 febrile neutropenia occurred in 25% of patients on decitabine versus 7% of patients on BSC; grade 3 to 4 infections occurred in 57% and 52% of patients on decitabine and BSC, respectively. Decitabine treatment was associated with improvements in patient-reported quality-of-life (QOL) parameters.ConclusionDecitabine administered in 6-week cycles is active in older patients with higher-risk MDS, resulting in improvements of OS and AMLFS (nonsignificant), of PFS and AML transformation (significant), and of QOL. Short MDS duration was an independent adverse prognosticator.