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Ann Oncol. 2013 Dec;24(12):2943-52. doi: 10.1093/annonc/mdt292. Epub 2013 Aug 6.

Incidence and risk of hemorrhagic events with vascular endothelial growth factor receptor tyrosine-kinase inhibitors: an up-to-date meta-analysis of 27 randomized controlled trials.

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  • 1Medical Oncology Unit, Oncology Department, the Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.

Abstract

BACKGROUND:

We aimed at determining the overall incidence and risk of hemorrhagic events associated with vascular endothelial growth factor receptor-tyrosine-kinase inhibitors (VEGFR-TKIs).

METHODS:

We searched PubMed, EMBASE and Cochrane library databases for relevant prospective, randomized controlled trials (RCTs). Statistical analyses were conducted to calculate the summary incidence, relative risks (RRs) and 95% confidence intervals (CIs) by using either random-effects or fixed-effects models according to the heterogeneity of included studies.

RESULTS:

The overall incidence of all-grade and high-grade hemorrhagic events was 9.1% (95% CI: 6.8-12.1%) and 1.3% (95% CI 0.8% to 2.1%), respectively. And the use of VEGFR-TKIs was associated with an increased risk of hemorrhagic events, with a relative risk (RR) of 1.67 (95% CI 1.19-2.33, P = 0.003), but not for high-grade hemorrhagic events (RR 1.23, 95% CI 0.86-1.77, P = 0.25). The risk of developing all-grade hemorrhagic events varied significantly with tumor types (P < 0.001) and different VEGFR-TKIs (P < 0.001). Additionally, the most common causes of all-grade hemorrhagic events were hemoptysis (48.6%) and epistaxis (20.7%), while hemoptysis (41.8%) and CNS hemorrhage (13.4%) was the most common cause of high-grade hemorrhagic events.

CONCLUSIONS:

While the use of VEGFR-TKIs is associated with a significantly increased risk of developing hemorrhagic events in cancer patients, this is primarily for lower grade events.

KEYWORDS:

VEGFR-TKIs; cancer; hemorrhagic events; meta-analysis

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