Meta-Analysis of Randomized Controlled Trials for the Incidence and Risk of Treatment-Related Mortality in Patients With Cancer Treated With Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitors

被引:153
作者
Schutz, Fabio A. B. [2 ,4 ]
Je, Youjin [3 ]
Richards, Christopher J. [2 ]
Choueiri, Toni K. [1 ,2 ]
机构
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA
[2] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA
[3] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA
[4] Hosp Sao Jose & Beneficencia Portuguesa Sao Paulo, Sao Paulo, Brazil
关键词
FOOT SKIN REACTION; PHASE-III; RENAL-CELL; DOUBLE-BLIND; SORAFENIB; SUNITINIB; CARCINOMA; ANGIOGENESIS; BEVACIZUMAB; CARBOPLATIN;
D O I
10.1200/JCO.2011.37.1195
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have become the cornerstone in the treatment of several malignancies. These drugs have also been associated with an increase in the risk of potentially life-threatening adverse events, such as arterial thrombotic events, bleeding, congestive heart failure, and others. We performed an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in patients with cancer treated with VEGFR TKIs. Methods MEDLINE and PubMed databases were searched for articles published from January 1966 to February 2011. Eligible studies were limited to trials of US Food and Drug Administration-approved VEGFR TKIs (pazopanib, sunitinib, and sorafenib) that reported on patients with cancer with any primary tumor type, randomized design, and adequate safety profile. Statistical analyses were conducted to calculate the summary incidence, relative risk (RR), and 95% CIs by using random-effects or fixed-effects models on the basis of the heterogeneity of included studies. Results In all, 4,679 patients from 10 randomized controlled trials (RCTs) were included, with 2,856 from sorafenib, 1,388 from sunitinib, and 435 from pazopanib trials. The incidence of FAEs related to VEGFR TKIs was 1.5% (95% CI, 0.8% to 2.4%) with an RR of 2.23 (95% CI, 1.12 to 4.44; P = .023) compared with control patients. On subgroup analysis, no difference in the rate of FAEs was found between different VEGFR TKIs or tumor types. No evidence of publication bias was observed. Conclusion In a meta-analysis of RCTs, the use of VEGFR TKIs was associated with an increased risk of FAEs compared with control patients. J Clin Oncol 30: 871-877. (C) 2012 by American Society of Clinical Oncology
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页码:871 / 877
页数:7
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