Division of Hematology and Medical Oncology, Department of Medicine, Stony Brook University Medical Center, Stony Brook, New York, USA.
Acta Oncol. 2010 Apr;49(3):287-97. doi: 10.3109/02841860903524396.
The risk of cardiovascular toxicities is a serious concern with the increased application of angiogenesis inhibitors in current cancer therapy. Arterial thromboembolic events (ATE) were associated with bevacizumab, an antibody against vascular endothelial growth factor. To determine the risk of ATE including cardiac ischemia and stroke, a systematic review and meta-analysis of published randomized controlled trials (RCTs) was performed.
We searched the databases of PubMed, Web of Science, and American Society of Clinical Oncology conferences to identify relevant clinical trials up to May, 2009. Eligible studies included prospective RCTs in which bevacizumab was compared to a control concurrently in combination with standard anti-neoplastic therapy. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models.
A total of 12 617 patients with a variety of advanced solid tumors from 20 RCTs were included for analysis. The incidences of all-grade and high-grade ATE in patients receiving bevacizumab were 3.3% (95% CI, 2.0-5.6%) and 2.0% (95% CI, 1.7-2.5) respectively. Patients treated with bevacizumab had a significantly increased risk of ATE with an RR of 1.44 (95% CI, 1.08-1.91; p=0.013) compared with controls. The risk similarly increased for bevacizumab at 2.5 and 5 mg/kg/week; in addition, significantly increased risks were observed in patients with renal cell cancer (RR, 3.72, 95% CI, 1.15-12.04; p=0.029) and colorectal cancer (RR, 1.89, 95% CI, 1.28-2.80, p=0.001). Notably, the risk of high-grade cardiac ischemia with bevacizumab was significantly higher than controls with an RR of 2.14 (95% CI, 1.12-4.08, p=0.021); however, the risk of ischemic stroke with bevacizumab was not significantly different from controls (RR, 1.37, 95% CI, 0.67-2.79, p=0.39).
Treatment with bevacizumab may significantly increase the risk of cardiac ischemic events in cancer patients.
随着血管生成抑制剂在癌症治疗中的广泛应用，心血管毒性的风险成为一个严重的问题。贝伐单抗是一种抗血管内皮生长因子的抗体，与动脉血栓栓塞事件（ATE）相关。为了确定包括心肌缺血和中风在内的 ATE 风险，我们对已发表的随机对照试验（RCT）进行了系统评价和荟萃分析。
我们检索了 PubMed、Web of Science 和美国临床肿瘤学会会议数据库，以确定截至 2009 年 5 月的相关临床试验。合格的研究包括贝伐单抗与标准抗肿瘤治疗联合应用的前瞻性 RCT，同时与对照进行比较。使用随机效应或固定效应模型计算总发生率、相对风险（RR）和 95%置信区间（CI）。
共有 20 项 RCT 的 12617 名患有各种晚期实体瘤的患者纳入分析。接受贝伐单抗治疗的患者发生所有级别和高级别 ATE 的发生率分别为 3.3%（95%CI，2.0-5.6%）和 2.0%（95%CI，1.7-2.5%）。与对照组相比，接受贝伐单抗治疗的患者 ATE 的风险显著增加，RR 为 1.44（95%CI，1.08-1.91；p=0.013）。贝伐单抗 2.5 和 5mg/kg/周的风险也同样增加；此外，在肾细胞癌（RR，3.72，95%CI，1.15-12.04；p=0.029）和结直肠癌（RR，1.89，95%CI，1.28-2.80，p=0.001）患者中观察到显著增加的风险。值得注意的是，贝伐单抗治疗的高级别心脏缺血风险显著高于对照组，RR 为 2.14（95%CI，1.12-4.08，p=0.021）；然而，贝伐单抗治疗的缺血性中风风险与对照组无显著差异（RR，1.37，95%CI，0.67-2.79，p=0.39）。
贝伐单抗治疗可能会显著增加癌症患者发生心脏缺血事件的风险。
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