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Review
. 2023 Aug 1:14:1231401.
doi: 10.3389/fphar.2023.1231401. eCollection 2023.

Oxaliplatin-induced peripheral neurotoxicity in colorectal cancer patients: mechanisms, pharmacokinetics and strategies

Fang Cheng  1 , Ruoqi Zhang  1 , Chen Sun  1 , Qian Ran  1 , Cuihan Zhang  1 , Changhong Shen  1 , Ziqing Yao  1 , Miao Wang  1 , Lin Song  2 , Cheng Peng  1
Affiliations
Review

Oxaliplatin-induced peripheral neurotoxicity in colorectal cancer patients: mechanisms, pharmacokinetics and strategies

Fang Cheng et al. Front Pharmacol. .

Abstract

Oxaliplatin-based chemotherapy is a standard treatment approach for colorectal cancer (CRC). However, oxaliplatin-induced peripheral neurotoxicity (OIPN) is a severe dose-limiting clinical problem that might lead to treatment interruption. This neuropathy may be reversible after treatment discontinuation. Its complicated mechanisms are related to DNA damage, dysfunction of voltage-gated ion channels, neuroinflammation, transporters, oxidative stress, and mitochondrial dysfunction, etc. Several strategies have been proposed to diminish OIPN without compromising the efficacy of adjuvant therapy, namely, combination with chemoprotectants (such as glutathione, Ca/Mg, ibudilast, duloxetine, etc.), chronomodulated infusion, dose reduction, reintroduction of oxaliplatin and topical administration [hepatic arterial infusion chemotherapy (HAIC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), and hyperthermic intraperitoneal chemotherapy (HIPEC)]. This article provides recent updates related to the potential mechanisms, therapeutic strategies in treatment of OIPN, and pharmacokinetics of several methods of oxaliplatin administration in clinical trials.

Keywords: adverse reaction; colorectal cancer; mechanism; oxaliplatin; peripheral neurotoxicity; pharmacokinetics; therapeutic strategies.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Figure 1 was created by Figdraw (www.figdraw.com).

Figures

FIGURE 1
FIGURE 1
OIPN is related to mechanisms of DNA damage, dysfunction of voltage-gated ion channels, neuroinflammation, transporters, oxidative stress, and mitochondrial dysfunction.
FIGURE 2
FIGURE 2
Administration routes of oxaliplatin and potential treatment options for OIPN in patients with CRC.
See this image and copyright information in PMC

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