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Review
. 2021 Aug 13;22(16):8733.
doi: 10.3390/ijms22168733.

Preclinical and Clinical Evidence of Therapeutic Agents for Paclitaxel-Induced Peripheral Neuropathy

Affiliations
Review

Preclinical and Clinical Evidence of Therapeutic Agents for Paclitaxel-Induced Peripheral Neuropathy

Takehiro Kawashiri et al. Int J Mol Sci. .

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: adverse effects; clinical evidence; paclitaxel; peripheral neuropathy; preclinical data.

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Conflict of interest statement

The authors declare that they have no conflict of interest to this work.

References

    1. Ozols R.F., Bundy B.N., Greer B.E., Fowler J.M., Clarke-Pearson D., Burger R.A., Mannel R.S., DeGeest K., Hartenbach E.M., Baergen R. Phase III Trial of Carboplatin and Paclitaxel Compared with Cisplatin and Paclitaxel in Patients with Optimally Resected Stage III Ovarian Cancer: A Gynecologic Oncology Group Study. J. Clin. Oncol. 2003;21:3194–3200. doi: 10.1200/JCO.2003.02.153. - DOI - PubMed
    1. Du Bois A., Lück H.-J., Meier W., Adams H.-P., Möbus V., Costa S., Bauknecht T., Richter B., Warm M., Schröder W., et al. A Randomized Clinical Trial of Cisplatin/Paclitaxel Versus Carboplatin/Paclitaxel as First-Line Treatment of Ovarian Cancer. J. Natl. Cancer Inst. 2003;95:1320–1329. doi: 10.1093/jnci/djg036. - DOI - PubMed
    1. Ohe Y., Ohashi Y., Kubota K., Tamura T., Nakagawa K., Negoro S., Nishiwaki Y., Saijo N., Ariyoshi Y., Fukuoka M. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann. Oncol. 2006;18:317–323. doi: 10.1093/annonc/mdl377. - DOI - PubMed
    1. Socinski M.A., Bondarenko I., Karaseva N.A., Makhson A.M., Vynnychenko I., Okamoto I., Hon J.K., Hirsh V., Bhar P., Zhang H., et al. Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Final Results of a Phase III Trial. J. Clin. Oncol. 2012;30:2055–2062. doi: 10.1200/JCO.2011.39.5848. - DOI - PubMed
    1. Sparano J.A., Wang M., Martino S., Jones V., Perez E.A., Saphner T., Wolff A., Sledge G.W., Wood W.C., Davidson N.E. Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer. N. Engl. J. Med. 2008;358:1663–1671. doi: 10.1056/NEJMoa0707056. - DOI - PMC - PubMed

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