Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism
Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism
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DOI：
10.1200/jco.2005.03.133
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发表时间：
2005-04-01
影响因子：
45.3
通讯作者：
Levine, MN
中科院分区：
文献类型：
--
作者：
Lee, AYY;Rickles, FR;Levine, MN
目的实验研究和间接临床证据表明，低分子肝素可能具有抗肿瘤作用。我们研究了低分子肝素达特肝素对活动性癌症和急性静脉血栓栓塞症患者生存率的影响。患者和方法在多中心、开放标签、随机对照试验中，对实体瘤和静脉血栓栓塞症患者随机分配达特肝素或香豆素衍生物治疗6个月后的生存数据进行分析。比较有和无转移恶性肿瘤患者治疗组12个月的全因死亡率。结果在12个月的随访期内，602例实体瘤和急性静脉血栓栓塞症患者中有356例死亡。在没有转移疾病的患者中，达肝素组12个月后死亡的概率为20%，而口服抗凝剂组为36%(风险比0.50；95%可信区间0.27至0.95；P=0.03)。在转移性癌症患者中，治疗组之间的死亡率没有差异(分别为72%和69%；风险比为1.1；95%CI为0.87至1.4；P=.46)。钙化肝素对有转移性疾病和无转移性疾病患者生存率的影响有统计学意义(P=0.02)。结论在发生急性静脉血栓栓塞症时没有转移性疾病的实体肿瘤患者中，相对于香豆素衍生物，使用达特肝素可以提高患者的生存率。有必要进行更多的研究来调查这些发现。(C)2005年，由美国临床肿瘤学会提供。
Purpose Experimental studies and indirect clinical evidence suggest that low molecular weight heparins may have antineoplastic effects. We investigated the influence of a low molecular weight heparin dalteparin on the survival of patients with active cancer and acute venous thromboembolism.Patients and Methods Survival data were examined in a posthoc analysis in patients with solid tumors and venous thromboembolism who were randomly assigned to dalteparin or a coumarin derivative for 6 months in a multicenter, open-label, randomized, controlled trial. All-cause mortality at 12 months was compared between treatment groups in patients with and without metastatic malignancy. The effect of dalteparin on survival was compared between the two patient subgroups.Results During the 12-month follow-up period, 356 of 602 patients with solid tumors and acute venous thromboembolism died. Among patients without metastatic disease, the probability of death at 12 months was 20% in the dalteparin group, as compared with 36% in the oral anticoagulant group (hazard ratio, 0.50; 95% CI, 0.27 to 0.95; P = .03). In patients with metastatic cancer, no difference in mortality between the treatment groups was observed (72% and 69%, respectively; hazard ratio, 1.1; 95% Cl, 0.87 to 1.4; P = .46). The observed effects of calteparin on survival were statistically significantly different between patients with and without metastatic disease (P = .02).Conclusion The use of dalteparin relative to coumarin derivatives was associated with improved survival in patients with solid tumors who did not have metastatic disease at the time of an acute venous thromboembolic event. Additional studies are warranted to investigate these findings. (c) 2005 by American Society of Clinical Oncology.