Investigation of drugs affecting hypertension in bevacizumab‐treated patients and examination of the impact on the therapeutic effect

Investigation of drugs affecting hypertension in bevacizumab‐treated patients and examination of the impact on the therapeutic effect

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...

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Published in:Cancer medicine (Malden, MA) Vol. 10; no. 1; pp. 164 - 172
Main Authors: Yagi, Kenta, Mitstui, Marin, Zamami, Yoshito, Niimura, Takahiro, Izawa‐Ishizawa, Yuki, Goda, Mitsuhiro, Chuma, Masayuki, Fukunaga, Kimiko, Shibata, Takahiro, Ishida, Shunsuke, Sakurada, Takumi, Okada, Naoto, Hamano, Hirofumi, Horinouchi, Yuya, Ikeda, Yasumasa, Yanagawa, Hiroaki, Ishizawa, Keisuke
Format: Journal Article
Language:English
Published: United States John Wiley & Sons, Inc 01-01-2021
John Wiley and Sons Inc
Subjects:
Age
Bevacizumab
Blood pressure
Cancer therapies
Chemotherapy
Clinical Cancer Research
Colorectal cancer
Colorectal carcinoma
Disease control
Drugs
FAERS
Gene expression
gene expression omnibus
Hypertension
Immunotherapy
Medical prognosis
Metastasis
Monoclonal antibodies
Omeprazole
Original Research
Patients
proton pump inhibitor
Proton pump inhibitors
Solid tumors
Targeted cancer therapy
Vascular endothelial growth factor
gene expression omnibus
bevacizumab
FAERS
colorectal cancer
hypertension
proton pump inhibitor
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Summary: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. The use of PPIs prevents hypertension in bevacizumab‐treated patients. However, it may reduce the anti‐tumor effect of bevacizumab by inducing the expression of VEGF.
Bibliography:Funding information
This research was supported by the Japan Research Foundation for Clinical Pharmacology Grant (Grant number 2018A10) and the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant number 18K06785)
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ISSN:2045-7634
2045-7634
DOI:10.1002/cam4.3587