JAMA:贫血药会增加癌症贫血患者静脉血栓和死亡风险

据2月27日《美国医学协会期刊》（JAMA）上的一则研究显示，应用一类叫作红血球生成-刺激剂（ESAs）的药物来治疗癌症病人的贫血与静脉血栓栓塞性疾病（即在下肢深静脉或肺部血管内血块生成）及死亡风险增加有关。

ESAs 中的erythropoietin 和 darbepoetin被广泛用来治疗癌症病患的贫血症。根据文章中的背景资讯，有研究指出，使用这些药物可能会增加深静脉血栓栓塞性疾病（VTE）的风险，但是，这些药物是否与死亡风险的增加有关则不清楚。

美国西北大学医学院的Charles L. Bennett及其同僚对第三期临床试验进行了审查，以调查癌症病患使用ESA来治疗贫血的VTE发生率及相关的死亡情况。

研究人员找到了51项临床试验的1万3611名病患并对其存活情况进行了调查。对这些数据的分析显示，癌症病患在用ESA治疗后，其死亡风险比对照（即安慰剂）组的受试者显著要高。

研究人员对38项临床试验中的8172名病患的静脉血栓栓塞性疾病进行了评估。研究人员发现，在接受ESA治疗的病人中，其发生VTE的风险（在4610位接受ESA治疗的病患中发生了334次VTE事件 vs. 在3562名对照组病患中出现173次VTE事件）会显著增加（57%）。

生物谷推荐原始出处:

（JAMA），2008;299(8):914-924，Charles L. Bennett，Michael Henke

Venous Thromboembolism and Mortality Associated With Recombinant Erythropoietin and Darbepoetin Administration for the Treatment of Cancer-Associated Anemia

Charles L. Bennett, MD, PhD; Samuel M. Silver, MD, PhD; Benjamin Djulbegovic, MD, PhD; Athena T. Samaras, BA; C. Anthony Blau, MD; Kara J. Gleason, BS; Sara E. Barnato, MD; Kathleen M. Elverman; D. Mark Courtney, MD; June M. McKoy, MD, MPH, JD; Beatrice J. Edwards, MD; Cara C. Tigue, BA; Dennis W. Raisch, PhD; Paul R. Yarnold, PhD; David A. Dorr, MD, MS; Timothy M. Kuzel, MD; Martin S. Tallman, MD; Steven M. Trifilio, RPh; Dennis P. West, PhD; Stephen Y. Lai, MD, PhD; Michael Henke, MD

Context The erythropoiesis-stimulating agents (ESAs) erythropoietin and darbepoetin are licensed to treat chemotherapy-associated anemia in patients with nonmyeloid malignancies. Although systematic overviews of trials have identified venous thromboembolism (VTE) risks, none have identified mortality risks with ESAs.

Objective To evaluate VTE and mortality rates associated with ESA administration for the treatment of anemia among patients with cancer.

Data Sources A published overview from the Cochrane Collaboration (search dates: January 1, 1985-April 1, 2005) and MEDLINE and EMBASE databases (key words: clinical trial, erythropoietin, darbepoetin, and oncology), the public Web site of the US Food and Drug Administration and ESA manufacturers, and safety advisories (search dates: April 1, 2005-January 17, 2008).

Study Selection Phase 3 trials comparing ESAs with placebo or standard of care for the treatment of anemia among patients with cancer.

Data Extraction Mortality rates, VTE rates, and 95% confidence intervals (CIs) were extracted by 3 reviewers from 51 clinical trials with 13 611 patients that included survival information and 38 clinical trials with 8172 patients that included information on VTE.

Data Synthesis Patients with cancer who received ESAs had increased VTE risks (334 VTE events among 4610 patients treated with ESA vs 173 VTE events among 3562 control patients; 7.5% vs 4.9%; relative risk, 1.57; 95% CI, 1.31-1.87) and increased mortality risks (hazard ratio, 1.10; 95% CI, 1.01-1.20).

Conclusions Erythropoiesis-stimulating agent administration to patients with cancer is associated with increased risks of VTE and mortality. Our findings, in conjunction with basic science studies on erythropoietin and erythropoietin receptors in solid cancers, raise concern about the safety of ESA administration to patients with cancer.