Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials
Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials
复制标题
DOI：
10.1016/s1470-2045(09)70222-0
复制
发表时间：
2009-10-01
期刊：
影响因子：
51.1
通讯作者：
Choueiri, Toni K.
中科院分区：
文献类型：
--
作者：
Je, Youjin;Schutz, Fabio A. B.;Choueiri, Toni K.
背景舒尼替尼和索拉非尼是用于多种癌症的口服血管内皮生长因子受体（VEGFR）酪氨酸激酶抑制剂。出血已被描述与这些药物，但总体风险仍不清楚。我们做了一个系统的回顾和荟萃分析，以计算与使用舒尼替尼和索拉非尼的发病率和相对风险。方法我们搜索PubMed（从1966年1月至2009年4月）和美国临床肿瘤学会和欧洲医学肿瘤学会（2004-09年）的相关临床试验的会议记录。符合条件的研究包括2期和3期试验以及扩大使用项目。统计分析进行计算汇总发生率，相对风险，和95%CI，使用随机效应或固定效应模型的异质性纳入study.Findings的基础上，选择23项试验进行荟萃分析，共产生6779例患者。出血事件（所有级别）的发生率为16.7%（95% CI 12.7-21.5），高级别事件的发生率为2.4%（1.6-3.9）。与舒尼替尼和索拉非尼相关的所有级别出血事件的相对风险（仅针对随机对照试验）为2.0（1.14-3.49; p=0.015）。我们的分析也分层潜在的恶性疾病（肾细胞癌与非肾细胞癌）和代理使用，但没有差异recorded.Interpretation治疗与VEGFR酪氨酸激酶抑制剂舒尼替尼和索拉非尼是与出血的风险显着增加。
Background Sunitinib and sorafenib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors used in various cancers. Bleeding has been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to calculate the incidence and relative risk associated with use of sunitinib and sorafenib.Methods We searched PubMed (from January, 1966, to April, 2009) and meeting proceedings of the American Society of Clinical Oncology and the European Society of Medical Oncology (2004-09) for relevant clinical trials. Eligible studies included phase 2 and 3 trials and expanded-access programmes. Statistical analyses were done to calculate summary incidences, relative risks, and 95% CI, using random-effects or fixed-effects models based on the heterogeneity of included studies.Findings 23 trials were selected for the meta-analysis, yielding a total of 6779 patients. The incidence of bleeding events (all grades) was 16.7% (95% CI 12.7-21.5), and that of high-grade events was 2.4% (1.6-3.9). The relative risk of all-grade bleeding events associated with sunitinib and sorafenib (for randomised controlled trials only) was 2.0 (1.14-3.49; p=0.015). Our analysis was also stratified by underlying malignant disease (renal-cell carcinoma vs non-renal-cell carcinoma) and agent used, but no differences were recorded.Interpretation Treatment with the VEGFR tyrosine-kinase inhibitors sunitinib and sorafenib is associated with a significant increase in risk of bleeding.