Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials
Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials
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DOI：
10.1016/s0140-6736(09)60502-x
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发表时间：
2009-05-02
期刊：
影响因子：
168.9
通讯作者：
Engert, Andreas
中科院分区：
文献类型：
--
作者：
Bohlius, Julia;Schmidlin, Kurt;Engert, Andreas
背景红细胞生成刺激剂可以减少癌症患者的贫血，并可以改善他们的生活质量，但这些药物可能会增加死亡率。因此，我们对随机对照试验进行了荟萃分析，其中将这些药物加红细胞输注与单独输血预防或治疗癌症患者贫血进行了比较。 方法 独立统计学家使用固定效应和随机效应荟萃分析获得并分析了接受阿法依泊汀、β 依泊汀或阿法达贝泊汀治疗的患者的数据。分析是按意向治疗进行的。主要终点是活跃研究期间的死亡率和最长随访期间的总生存期（无论是否接受抗癌治疗）以及接受化疗的患者。相互作用测试用于确定红细胞生成刺激剂对预先指定的亚组死亡率影响的差异。结果分析了 53 项试验中总共 13 933 名癌症患者的数据。在活跃研究期间，共有 1530 名患者死亡，总计 4993 名患者死亡。红细胞生成刺激剂会增加活跃研究期间的死亡率（综合风险比 [cHR] 1.17，95% CI 1.06-1.30），并恶化总生存期（1.06，1.00-1.12），试验之间几乎没有异质性（活跃研究期间的死亡率 I-2 0%，p=0.87，I-2 7.1%，p=0.33）总体生存）。 38 项试验招募了 10 441 名接受化疗的患者。活跃研究期间死亡率的 cHR 为 1.10 (0.98-1.24)，总生存期的 cHR 为 1.04 (0.97-1.11)。几乎没有证据表明接受不同抗癌治疗的患者进行的试验之间存在差异（交互作用p = 0.42）。 解释 癌症患者接受红细胞生成刺激剂治疗会增加活跃研究期间的死亡率并恶化总生存期。与这些药物治疗相关的死亡风险增加应与其益处相平衡。
Background Erythropoiesis-stimulating agents reduce anaemia in patients with cancer and could improve their quality of life, but these drugs might increase mortality. We therefore did a meta-analysis of randomised controlled trials in which these drugs plus red blood cell transfusions were compared with transfusion alone for prophylaxis or treatment of anaemia in patients with cancer.Methods Data for patients treated with epoetin alfa, epoetin beta, or darbepoetin alfa were obtained and analysed by independent statisticians using fixed-effects and random-effects meta-analysis. Analyses were by intention to treat. Primary endpoints were mortality during the active study period and overall survival during the longest available follow-up, irrespective of anticancer treatment, and in patients given chemotherapy. Tests for interactions were used to identify differences in effects of erythropoiesis-stimulating agents on mortality across prespecified subgroups.Findings Data from a total of 13 933 patients with cancer in 53 trials were analysed. 1530 patients died during the active study period and 4993 overall. Erythropoiesis-stimulating agents increased mortality during the active study period (combined hazard ratio [cHR] 1.17, 95% CI 1.06-1.30) and worsened overall survival (1.06, 1.00-1.12), with little heterogeneity between trials (I-2 0%, p=0.87 for mortality during the active study period, and I-2 7.1%, p=0.33 for overall survival). 10 441 patients on chemotherapy were enrolled in 38 trials. The cHR for mortality during the active study period was 1.10 (0.98-1.24), and 1.04 (0.97-1.11) for overall survival. There was little evidence for a difference between trials of patients given different anticancer treatments (p for interaction=0.42).Interpretation Treatment with erythropoiesis-stimulating agents in patients with cancer increased mortality during active study periods and worsened overall survival. The increased risk of death associated with treatment with these drugs should be balanced against their benefits.