Investigation of Drugs Affecting Hypertension in Bevacizumab-treated Patients and Examination of the Impact on the Therapeutic Effect

Overview

Journal Cancer Med

Specialty Oncology

Date 2020 Nov 24

PMID 33231381

Citations 8

Authors

Kenta Yagi

Marin Mitstui

Yoshito Zamami

Takahiro Niimura

Yuki Izawa-Ishizawa

Mitsuhiro Goda

Masayuki Chuma

Kimiko Fukunaga

Takahiro Shibata

Shunsuke Ishida

Takumi Sakurada

Naoto Okada

Hirofumi Hamano

Yuya Horinouchi

Yasumasa Ikeda

Hiroaki Yanagawa

Keisuke Ishizawa

Affiliations

Soon will be listed here.

Abstract

Background: In patients treated with bevacizumab, hypertension may be a biomarker of therapeutic efficacy. However, it is not clear whether drugs that control blood pressure influence bevacizumab's efficacy. In this study, we investigated drugs that may affect hypertension in bevacizumab-treated patients and examined the impact on the therapeutic effect.

Patients And Methods: We analyzed 3,724,555 reports from the third quarter of 2010 to the second quarter of 2015. All data were obtained from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) analysis. In this retrospective cohort study, we investigated a total of 58 patients diagnosed with colorectal cancer and treated for the first time with bevacizumab containing XELOX or mFOLFOX6 at The University of Tokushima Hospital between January 2010 and December 2015. The effect of the treatment was evaluated according to Response Evaluation Criteria in Solid Tumors version 1.0. Thereafter, the effect was confirmed using Gene Expression Omnibus (GEO) and cultured cells.

Results: There are few reports in FAERS of hypertension in patients treated with omeprazole on bevacizumab. Based on the chart review, patients who used proton pump inhibitors (PPI) had a lower response to treatment than those who did not (response rate: 25% vs 50%). Furthermore, experiments on GEO and cell lines suggested that induction of vascular endothelial growth factor (VEGF) gene expression by PPIs is the cause of the reduced therapeutic effect.

Conclusion: PPIs prevent hypertension in bevacizumab-treated patients but may reduce bevacizumab's anti-tumoral effects by inducing VEGF expression.

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