Cheng Fang, Zhang Ruoqi, Sun Chen, Ran Qian, Zhang Cuihan, Shen Changhong, Yao Ziqing, Wang Miao, Song Lin, Peng Cheng
State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Department of Pharmacy, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China.
Front Pharmacol. 2023 Aug 1;14:1231401. doi: 10.3389/fphar.2023.1231401. eCollection 2023.
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, 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, ), 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.
基于奥沙利铂的化疗是结直肠癌（CRC）的标准治疗方法。然而，奥沙利铂诱导的周围神经毒性（OIPN）是一个严重的剂量限制性临床问题，可能导致治疗中断。这种神经病变在停药后可能是可逆的。其复杂的机制与DNA损伤、电压门控离子通道功能障碍、神经炎症、转运体、氧化应激和线粒体功能障碍有关。已经提出了几种在不影响辅助治疗疗效的情况下减少OIPN的策略，即与化学保护剂（如谷胱甘肽、钙/镁、异丁司特、度洛西汀）联合使用、时辰调制输注、剂量减少、重新引入奥沙利铂以及局部给药[肝动脉灌注化疗（HAIC）、加压腹腔内气溶胶化疗（PIPAC）和热腹腔内化疗（HIPEC）]。本文提供了与OIPN潜在机制、治疗策略以及临床试验中几种奥沙利铂给药方法的药代动力学相关的最新进展。
