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Preventive Effects of Renin-angiotensin System Inhibitors on Oxaliplatin-induced Peripheral Neuropathy: A Retrospective Observational Study
Authors:Mami Uchida  Hitoshi Kawazoe  Shingo Takatori  Hiroyuki Namba  Ryuji Uozumi  Akihiro Tanaka  Hiromu Kawasaki  Hiroaki Araki
Institution:1. Department of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime, Japan;2. Division of Pharmacy, Ehime University Hospital, Shitsukawa, Toon, Ehime, Japan;3. Division of Pharmaceutical Care Sciences, Keio University Graduate School of Pharmaceutical Sciences, 1-5-30 Shibakoen, Minato-ku, Tokyo, Japan;4. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan;5. Faculty of Pharmaceutical Sciences, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama, Japan
Abstract:

Purpose

Oxaliplatin-induced peripheral neuropathy has remained an unresolved issue in clinical practice. Our previous study hypothesized that inhibition of the renin-angiotensin system (RAS) may produce a preventive effect on oxaliplatin-induced neuropathy. The aim of this study was to clarify whether RAS inhibitors prevent oxaliplatin-induced peripheral neuropathy.

Methods

This study retrospectively analyzed data from cancer patients who had received chemotherapy including oxaliplatin and were treated with or without RAS inhibitors. This retrospective observational study was conducted at Ehime University Hospital using electronic medical records from May 2009 to December 2016. The primary end point was the incidence of severe peripheral neuropathy during or after oxaliplatin treatment, according to the Common Terminology Criteria for Adverse Events, version 4.0. A multivariate Cox proportional hazards model analysis was used to identify risk factors.

Findings

A total of 150 patients were included in the study. The estimated incidence of peripheral neuropathy was 36.9% and 91.7% in the RAS inhibitor group and the non–RAS inhibitor group, respectively. The multivariate analysis using a Cox proportional hazards model showed that the RAS inhibitor group was slightly associated with a decreased risk of neurotoxicity (adjusted hazard ratio, 0.42 95% CI, 0.18–0.99]; P?=?0.048).

Implications

The present findings suggest that RAS inhibitors have the ability to prevent oxaliplatin-induced peripheral neuropathy.
Keywords:angiotensin-converting enzyme inhibitor  angiotensin receptor blocker  chemotherapy-induced peripheral neuropathy  oxaliplatin  renin-angiotensin system inhibitors
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