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Preclinical and Clinical Evidence of Therapeutic Agents for Paclitaxel-Induced Peripheral Neuropathy
Authors:Takehiro Kawashiri  Mizuki Inoue  Kohei Mori  Daisuke Kobayashi  Keisuke Mine  Soichiro Ushio  Hibiki Kudamatsu  Mayako Uchida  Nobuaki Egashira  Takao Shimazoe
Affiliation:1.Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan; (M.I.); (K.M.); (D.K.); (K.M.); (H.K.); (T.S.);2.Department of Pharmacy, Okayama University Hospital, Okayama 700-8558, Japan;3.Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyoto 610-0395, Japan;4.Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan;
Abstract:Paclitaxel is an essential drug in the chemotherapy of ovarian, non-small cell lung, breast, gastric, endometrial, and pancreatic cancers. However, it frequently causes peripheral neuropathy as a dose-limiting factor. Animal models of paclitaxel-induced peripheral neuropathy (PIPN) have been established. The mechanisms of PIPN development 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 PIPN effects. This review summarizes the basic and clinical evidence for therapeutic or prophylactic effects for PIPN. In pre-clinical research, many reports exist of neuropathy inhibitors that target oxidative stress, inflammatory response, ion channels, transient receptor potential (TRP) channels, cannabinoid receptors, and the monoamine nervous system. Alternatively, very few drugs have demonstrated PIPN efficacy in clinical trials. Thus, enhancing translational research to translate pre-clinical research into clinical research is important.
Keywords:paclitaxel   peripheral neuropathy   preclinical data   clinical evidence   adverse effects
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