Randomized Trial of the Effect of the Low Molecular Weight Heparin Nadroparin on Survival in Patients With Cancer
Randomized Trial of the Effect of the Low Molecular Weight Heparin Nadroparin on Survival in Patients With Cancer
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DOI：
10.1200/jco.2010.31.9293
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发表时间：
2011-05-20
影响因子：
45.3
通讯作者：
Buller, Harry R.
中科院分区：
文献类型：
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作者：
van Doormaal, Frederiek F.;Di Nisio, Marcello;Buller, Harry R.
目的：早期研究表明，低分子量肝素可显著延长多种无静脉血栓栓塞的癌症患者的生存期。这项研究的目的是在一组更均匀的癌症患者中证实这些发现。在这项多中心、随机、开放标签的研究中，患有非小细胞肺癌（IIIB期）、激素难治性前列腺癌或局部晚期胰腺癌的患者在接受标准抗癌治疗的基础上，随机分配接受nadroparin治疗或不接受nadroparin治疗。在nadroparin组，皮下给予nadroparin 6周（2周治疗剂量，4周治疗剂量的一半）。患者有资格接受额外周期的nadroparin（治疗剂量2周，洗脱期4周）。结果是总生存期、进展时间和大出血。所有研究结果均由一个独立的盲法委员会裁决。结果共244例患者被分配到nadroparin组，259例患者被分配到对照组。接受nadroparin治疗组的中位生存期为13.1个月，而未接受治疗组的中位生存期为11.9个月（风险比为0.94；95% CI为0.75至1.18，根据癌症类型调整）。观察到进展时间无差异。nadroparin组大出血发生率为4.1%，对照组为3.5%。结论：本研究未显示nadroparin在晚期前列腺癌、肺癌或胰腺癌患者中的生存获益。鉴于该领域正在进行的研究和先前的数据，低分子量肝素在癌症生存中的作用仍不明确。
PurposeEarlier studies showed that low molecular weight heparin significantly prolongs the survival of a wide variety of patients with cancer without venous thromboembolism. This study was designed to confirm these findings in a more homogeneous group of patients with cancer.Patients and MethodsIn this multicenter, randomized, open-label study, patients with non-small-cell lung cancer (stage IIIB), hormone-refractory prostate cancer, or locally advanced pancreatic cancer were randomly assigned to nadroparin or to no nadroparin in addition to their standard anticancer treatment. In the nadroparin arm, subcutaneous nadroparin was administered for 6 weeks (2 weeks at therapeutic dose, and 4 weeks at half therapeutic dose). The patients were eligible to receive additional cycles of nadroparin (2 weeks at therapeutic dose, and 4 weeks of washout period). Outcomes were overall survival, time to progression, and major bleeding. All study outcomes were adjudicated by an independent, blinded committee.ResultsA total of 244 patients were allocated to nadroparin, and 259 were allocated to the control group. A median survival of 13.1 months was observed in the nadroparin recipients compared with 11.9 months in the no-treatment arm (hazard ratio, 0.94; 95% CI, 0.75 to 1.18, adjusted for cancer type). No difference in time to progression was observed. The number of major bleedings was comparable at 4.1% in the nadroparin set and 3.5% in the control set.ConclusionThis study did not show a survival benefit of nadroparin in patients with advanced prostate, lung, or pancreatic cancer. Given the ongoing studies in this area and the previous data, the role of low molecular weight heparins in cancer survival remains undefined.