A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-tine therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome
A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-tine therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome
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DOI：
10.1182/blood-2007-11-124602
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发表时间：
2008-09-01
期刊：
影响因子：
20.3
通讯作者：
Kantarjian, Hagop M.
中科院分区：
文献类型：
--
作者：
Faderl, Stefan;Ravandi, Farhad;Kantarjian, Hagop M.
我们先前报道了氯法拉滨和阿糖胞苷联合治疗AML的可行性。问题仍然是（1）这种组合的治疗优势和（2）低剂量氯法拉滨和阿糖胞苷在老年患者中的作用。我们在60岁及以上的既往未经治疗的AML患者中进行了一项适应性随机研究，比较低剂量氯法拉滨联合或不联合低剂量阿糖胞苷。患者接受氯法拉滨30 mg/m2静脉注射，每日1次，共5天，同时或不同时接受阿糖胞苷20 mg/m2皮下注射，每日1次，共14天作为诱导。巩固治疗包括3天氯法拉滨联合或不联合7天阿糖胞苷。入组了70例患者。中位年龄为71岁（范围：60-83岁）。16例患者接受氯法拉滨治疗，54例患者接受联合治疗。总体而言，56%的患者达到完全缓解（CR）。联合治疗的CR率显著更高（63% vs 31%; P = 0.025）。联合用药诱导死亡率为19%，氯法拉滨单药诱导死亡率为31%（P = 0.276）。联合治疗组的无事件生存率更高（7.1个月vs 1.7个月; P = 0.04），但总生存率不高（11.4个月vs 5.8个月; P = 0.1）。氯法拉滨联合低剂量阿糖胞苷的缓解率高于氯法拉滨单药治疗，但毒性相当。本试验在www.clinicaltrials.gov上注册，编号为NCT 00088218。
We previously reported the feasibility of clofarabine and cytarabine combinations in AML. Questions remain as to (1) the therapeutic advantage of this combination and (2) the role of lower doses of clofarabine and cytarabine in older patients. We have conducted an adaptively randomized study of lower-dose clofarabine with or without low-dose cytarabine in previously untreated patients with AML aged 60 years and older. Patients received 30 mg/m(2) clofarabine intravenously daily for 5 days with or without 20 mg/m(2) cytarabine subcutaneously daily for 14 days as induction. Consolidation consisted of 3 days of clofarabine with or without 7 days of cytarabine. Seventy patients were enrolled. The median age was 71 years (range, 60-83 years). Sixteen patients received clofarabine and 54 the combination. Overall, 56% achieved complete remission (CR). CR rate was significantly higher with the combination (63% vs 31%; P = .025). Induction mortality was 19% with the combination versus 31% with clofarabine alone (P = .276). The combination showed better event-free survival (7.1 months vs 1.7 months; P = .04), but not overall survival (11.4 months vs 5.8 months; P = .1). Clofarabine plus low-dose cytarabine has a higher response rate than clofarabine alone with comparable toxicity. This trial is registered at www.clinicaltrials.gov as no. NCT00088218.