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Increased risk of severe infections in cancer patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a meta-analysis

Authors Ma Q, Gu L, Ren Y, Zeng L, Gong T, Zhong D

Received 24 April 2015

Accepted for publication 25 May 2015

Published 28 August 2015 Volume 2015:8 Pages 2361—2374


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Editor who approved publication: Professor Daniele Santini

Qing Ma, Li-Yan Gu, Yao-Yao Ren, Li-Li Zeng, Ting Gong, Dian-Sheng Zhong

Department of Oncology, The General Hospital of Tianjin Medical University, Tianjin, People’s Republic of China

Background: Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) have been widely used in a variety of solid malignancies. Concerns have arisen regarding the risk of severe infections (≥grade 3) with use of these drugs, but the contribution of VEGFR-TKIs to infections is still unknown.
Methods: The databases of PubMed and abstracts presented at oncology conferences’ proceedings were searched for relevant studies from January 2000 to December 2014. Summary incidences, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were calculated by using either random-effects or fixed-effects models according to the heterogeneity of included studies.
Results: A total of 16,488 patients from 27 randomized controlled trials were included. The risk of developing severe (Peto OR 1.69, 95% CI: 1.45–1.96, P<0.001) and fatal infections (Peto OR 1.78, 95% CI: 1.13–2.81, P=0.013) was significantly increased in patients treated with VEGFR-TKIs when compared to controls. Exploratory subgroup analysis showed no effect of tumor types, phase of trials, or agent used on the Peto OR of severe infections. When stratified according to specific infectious events, the risks of high-grade febrile neutropenia, pneumonia, fever, and sepsis were increased compared with controls, with Peto ORs of 1.57 (95% CI: 1.30–1.88, P<0.001), 1.79 (95% CI: 1.29–2.49, P<0.001), 5.35 (95% CI: 1.47–19.51, P=0.011), and 3.68 (95% CI: 1.51–8.99, P=0.004), respectively. Additionally, VEGFR-TKIs significantly increased the risk of fatal sepsis (OR 3.66, 95% CI: 1.47–9.13, P=0.005) but not fatal pneumonia (OR 1.34, 95% CI: 0.80–2.25, P=0.26).
Conclusion: The use of VEGFR-TKIs significantly increases the risk of developing severe and fatal infectious events in cancer patients. A close monitoring for any signs of infections is recommended for patients treated with VEGFR-TKIs.

Keywords: VEGFR-TKIs, infections, cancer, randomized controlled trials, meta-analysis

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