Abstract
BackgroundVascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) have emerged as an effective targeted therapy in the treatment of cancer patients, the overall incidence and risk of proteinuria associated these drugs is unclear. We performed a systematic review and meta-analysis of published clinical trials to quantify the incidence and risk of proteinuria associated with VEGFR-TKIs.MethodologyDatabases from PubMed, Web of Science and abstracts presented at ASCO meeting up to May 31, 2013 were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating VEGFR-TKIs in cancer patients with adequate data on proteinuria. Statistical analyses were conducted to calculate the summary incidence, Odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies.Principal FindingsA total of 6,882 patients with a variety of solid tumors from 33 clinical trials were included in our analysis. The incidence of all-grade and high-grade (grade 3 or higher) proteinuria was 18.7% (95% CI, 13.3%–25.6%) and 2.4% (95% CI, 1.6%–3.7%), respectively. Patients treated with VEGFR-TKIs had a significantly increased risk of all-grade (OR 2.92, 95%CI: 1.09–7.82, p = 0.033) and high-grade proteinuria (OR 1.97, 95%CI: 1.01–3.84, p = 0.046) when compared to patients treated with control medication. No evidence of publication bias was observed.ConclusionsThe use of VEGFR-TKIs is associated with a significant increased risk of developing proteinuria. Physicians should be aware of this adverse effect and should monitor cancer patients receiving VEGFR-TKIs.
Highlights
Angiogenesis plays an important role in the growth, invasion, and metastasis of malignancies [1,2,3,4,5], and this process is mainly driven by vascular epithelial growth factor (VEGF)
Physicians should be aware of this adverse effect and should monitor cancer patients receiving VEGFR-TKIs
Our results showed that the use of VEGFR-TKIs significantly increased the risk of proteinuria in high-quality trials, but not for low-quality trials
Summary
Angiogenesis plays an important role in the growth, invasion, and metastasis of malignancies [1,2,3,4,5], and this process is mainly driven by vascular epithelial growth factor (VEGF). Therapies that inhibit the VEGF pathway, including VEGF monoclonal antibody bevacizumab and vascular epithelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) such as sorafenib, sunitinib, vandetanib, pazopanib axitinib, and regorafenib, have shown clinical efficacy in the treatment of several malignancies and have been approved for use in cancer treatments by regulatory agencies [9,10,11,12,13,14,15,16,17]. We conducted a systematic review of the literature to identify prospective clinical trials of VEGFR-TKIs and performed a meta-analysis of the published results to estimate the incidence and risk of developing proteinuria. Vascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) have emerged as an effective targeted therapy in the treatment of cancer patients, the overall incidence and risk of proteinuria associated these drugs is unclear. We performed a systematic review and meta-analysis of published clinical trials to quantify the incidence and risk of proteinuria associated with VEGFR-TKIs
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