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, 8 (31), 51492-51506
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Bevacizumab Significantly Increases the Risks of Hypertension and Proteinuria in Cancer Patients: A Systematic Review and Comprehensive Meta-Analysis

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Bevacizumab Significantly Increases the Risks of Hypertension and Proteinuria in Cancer Patients: A Systematic Review and Comprehensive Meta-Analysis

Tingting Zhao et al. Oncotarget.

Abstract

Published data regarding the overall risks and incidence of hypertension and proteinuria associated with bevacizumab were still unclear. To quantify the precise risks and incidence, we performed this comprehensive meta-analysis of 72 published clinical trials including 21902 cases and 20608 controls. The overall incidence, risk ratios (RRs), and 95% confidence intervals (95% CIs) were calculated using a fixed or random-effect model based on the heterogeneity. The incidence of all-grade and high-grade hypertension were 25.3% (95% CI: 21.5%-29.5%) and 8.2% (95% CI: 7%-9.8%) for patients treated with bevacizumab. And the incidence of all-grade and high-grade proteinuria were 18% (95% CI: 11.7%-26.6%) and 2.4% (95% CI: 1.8%-3.2%), respectively. Compared with controls, bevacizumab significantly increased the risks of all-grade (RR: 3.595, 95% CI: 2.952-4.378) and high-grade hypertension (RR: 5.173, 95% CI: 4.188-6.390). Obviously increased risks of all-grade (RR: 3.369, 95% CI: 2.492-4.556) and high-grade proteinuria (RR: 5.494, 95% CI: 3.991-7.564) were also observed. In the subgroup analysis, the risks of hypertension and proteinuria may significantly vary with bevacizumab dosage, cancer types and concomitant drugs. Whereas, no obvious difference were discovered when stratified based on phase of trials, age of patients, treatment line and duration. So, close monitor and effective management were highly recommended for the safe use of bevacizumab.

Keywords: bevacizumab; cancer; chemotherapy; hypertension; proteinuria.

Conflict of interest statement

CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Selection process for randomized–controlled trials (RCTs) included in the meta-analysis
Figure 2
Figure 2. RRs of high-grade hypertension for cancer patients who received (A) low-dose and (B) high-dose bevacizumab compared with controls
Figure 3
Figure 3
RRs of (A) all-grade hypertension and (B) all-grade proteinuria for cancer patients who received low-dose and high-dose bevacizumab compared with controls.
Figure 4
Figure 4
RRs of high-grade proteinuria for cancer patients who received (A) low-dose and (B) high-dose bevacizumab compared with controls.
Figure 5
Figure 5. Funnel-plot standard error based on the risk ratio for relative risk of (A) all-grade hypertension and (B) high-grade hypertension (C) all-grade proteinuria and (D) high-grade proteinuria

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