Therapeutic Agents for Oxaliplatin-Induced Peripheral Neuropathy; Experimental and Clinical Evidence.

Takehiro Kawashiri,Daisuke Kobayashi,Takao Shimazoe,Mizuki Inoue,Keisuke Mine,Soichiro Ushio,Mayako Uchida,Nobuaki Egashira

doi:10.3390/ijms22031393

Abstract

Oxaliplatin is an essential drug in the chemotherapy of colorectal, gastric, and pancreatic cancers, but it frequently causes peripheral neuropathy as a dose-limiting factor. So far, animal models of oxaliplatin-induced peripheral neuropathy have been established. The mechanisms of development of neuropathy induced by oxaliplatin have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory effects on neuropathy. In this review, we summarize the basic and clinical evidence for the therapeutic effects of oxaliplatin. In basic research, there are many reports of neuropathy inhibitors that target oxidative stress, inflammatory response, sodium channel, transient receptor potential (TRP) channel, glutamate nervous system, and monoamine nervous system. Alternatively, very few drugs have clearly demonstrated the efficacy for oxaliplatin-induced peripheral neuropathy in clinical trials. It is important to activate translational research in order to translate basic research into clinical research.

Highlights

Oxaliplatin is a platinum-based chemotherapeutic agent that is widely used as a standard treatment for colorectal, gastric, and pancreatic cancers, usually combined with other therapeutic agents such as fluorouracil, irinotecan, capecitabine, or tegafur, gimeracil and oteracil, it often causes severe peripheral neuropathy
Previous reports have suggested that voltage-gated ion channels and transient receptor potential channels are involved in oxaliplatin-induced acute neuropathy [4,5,6]
We reviewed the preclinical and clinical evidence for oxaliplatin-induced peripheral neuropathy

Summary

Introduction

Oxaliplatin is a platinum-based chemotherapeutic agent that is widely used as a standard treatment for colorectal, gastric, and pancreatic cancers, usually combined with other therapeutic agents such as fluorouracil, irinotecan, capecitabine, or tegafur, gimeracil and oteracil, it often causes severe peripheral neuropathy. Within a few hours to a few days after oxaliplatin administration, acute neuropathy, such as cold sensory disturbance in the limbs and perioral region, appears. Sensory deficits as chronic neuropathy, a dose-limiting factor, occur after repeated oxaliplatin administration [2,3]. These neuropathies remain a significant clinical problem with oxaliplatin chemotherapy because they can affect quality of life and lead to drug reductions or discontinuation. Previous reports have suggested that voltage-gated ion channels and transient receptor potential channels are involved in oxaliplatin-induced acute neuropathy [4,5,6]. No drugs have been recommended to prevent chemotherapy-induced peripheral neuropathy [10]. Since around 2000, animal models of chemotherapy-induced peripheral neuropathy, including oxaliplatin-induced

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Discussion

Conclusion