Akl E A, van Doormaal F F, Barba M, Kamath G, Kim S Y, Kuipers S, Middeldorp S, Yosuico V, Dickinson H O, Schünemann H J
State University of New York at Buffalo, Medicine, ECMC, CC-142, 462 Girder Street, Buffalo, New York, 14215, USA.
Cochrane Database Syst Rev. 2007 Jul 18(3):CD006652. doi: 10.1002/14651858.CD006652.
Basic research and clinical studies have generated the hypothesis that anticoagulation may improve survival in patients with cancer through an antitumour effect in addition to the antithrombotic effect.
To evaluate the efficacy and safety of heparin (including unfractionated heparin (UFH) and low molecular weight heparin (LMWH)) and fondaparinux to improve survival of patients with cancer.
A comprehensive search for studies of anticoagulation in cancer patients including (1) A January 2007 electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ISI the Web of Science; (2) Hand search of the American Society of Clinical Oncology and of the American Society of Hematology; (3) Checking of references of included studies; and (4) Use of "related article" feature in PubMed.
We included randomized controlled trials (RCTs) in cancer patients without clinical evidence of venous thromboembolism comparing UFH, LMWH or fondaparinux to no intervention or placebo and RCTs comparing two of the three agents of interest.
Using a standardized form we extracted in duplicate data on methodological quality, participants, interventions and outcomes of interest including all cause mortality, venous thrombosis, symptomatic pulmonary embolism, major bleeding and minor bleeding.
Of 3986 identified citations five RCTs fulfilled the inclusion criteria. In all included RCTs the intervention consisted of heparin ( either UFH or LMWH). The overall methodological quality of the included studies was acceptable. Overall, heparin therapy was associated with a statistically and clinically significant survival benefit (hazard ratio (HR) = 0.77; 95% CI: 0.65 to 0.91). In subgroup analyses, patients with limited small cell lung cancer experienced a clear survival benefit (HR = 0.56; 95% CI: 0.38 to 0.83). The survival benefit was not statistically significant for either patients with extensive small cell lung cancer (HR = 0.80; 95% CI: 0.60 to 1.06) or patients with advanced cancer (HR = 0.84; 95%: 0.68 to 1.03). The increased risk of bleeding with heparin was not statistically significant (RR = 1.78; 95% CI: 0.73 to 4.38).
AUTHORS' CONCLUSIONS: Heparin has a survival benefit in cancer patients in general, and in patients with limited small cell lung cancer in particular. Heparin might be particularly beneficial in cancer patients with limited cancer or a longer life expectancy. Future research should investigate the survival benefit of different types of anticoagulants (in different dosing, schedules and duration of therapy) in patients with different types and stages of cancers.
基础研究和临床研究提出了这样一种假说，即抗凝治疗除具有抗血栓形成作用外，还可能通过抗肿瘤作用提高癌症患者的生存率。
评估肝素（包括普通肝素（UFH）和低分子肝素（LMWH））以及磺达肝癸钠改善癌症患者生存率的疗效和安全性。
全面检索关于癌症患者抗凝治疗的研究，包括：（1）2007年1月对以下数据库进行电子检索：Cochrane对照试验中心注册库（CENTRAL）、医学索引（MEDLINE）、荷兰医学文摘数据库（EMBASE）以及科学引文索引（ISI）科学网；（2）手工检索美国临床肿瘤学会和美国血液学会的资料；（3）检查纳入研究的参考文献；（4）使用PubMed中的“相关文章”功能。
我们纳入了无静脉血栓栓塞临床证据的癌症患者的随机对照试验（RCT），这些试验比较了UFH、LMWH或磺达肝癸钠与未干预或安慰剂，以及比较三种相关药物中两种药物的RCT。
我们使用标准化表格，一式两份提取关于方法学质量、参与者、干预措施和感兴趣结局的数据，包括全因死亡率、静脉血栓形成、症状性肺栓塞、大出血和小出血。
在3986条检索到的文献中，有5项RCT符合纳入标准。在所有纳入的RCT中，干预措施均为肝素（UFH或LMWH）。纳入研究的总体方法学质量是可以接受的。总体而言，肝素治疗具有统计学和临床意义上的生存获益（风险比（HR）=0.77；95%置信区间（CI）：0.65至0.91）。在亚组分析中，局限性小细胞肺癌患者有明显的生存获益（HR = 0.56；95% CI：0.38至0.83）。广泛性小细胞肺癌患者（HR = 0.80；95% CI：0.60至1.06）或晚期癌症患者（HR = 0.84；95% CI：0.68至1.03）的生存获益无统计学意义。肝素导致出血风险增加无统计学意义（相对危险度（RR）=1.78；95% CI：0.73至4.38）。
肝素总体上对癌症患者有益，尤其对局限性小细胞肺癌患者有益。肝素可能对癌症局限或预期寿命较长的癌症患者特别有益。未来的研究应调查不同类型抗凝剂（不同剂量、给药方案和治疗持续时间）对不同类型和分期癌症患者的生存获益情况。
