An antimicrotubule agent, TZT-1027, does not induce neuropathologic alterations which are detected after administration of vincristine or paclitaxel in animal models

Toxicology Letters
T OgawaT Nakayama

Abstract

One of the major dose-limiting toxicities induced by antimicrotubule antitumor agents such as vinca alkaloids and taxanes is peripheral neuropathy. The neurotoxicity of TZT-1027 (a dolastatin 10 derivative antimicrotubule agent) was thus assessed using the animal models for antimicrotubule agent-induced neurotoxicity. Rabbits were intravenously given TZT-1027 or vincristine weekly for 5 weeks. In the mouse study, TZT-1027, vincristine or paclitaxel was intravenously given every 2 days and/or weekly. Despite the neuropathologic evidence such as myelinated axonal and fiber degeneration in the peripheral nerves and in the sensory tracts of the spinal cord following the treatment with vincristine or paclitaxel, no drug-induced alteration was observed in the TZT-1027 groups. Although there are reports that some other dolastatin derivatives with antimicrotubule activity showed no neurotoxic potential in humans, the present study represents the first demonstration in experimental animals that a dolastatin derivative has no, or at least a lower, neurotoxic potential compared to other antimicrotubule agents.

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Citations

Jun 4, 2013·The Journal of Pain : Official Journal of the American Pain Society·Haijun ZhangPatrick M Dougherty
Oct 19, 2011·Journal of the Peripheral Nervous System : JPNS·Jordi BrunaEsther Udina
May 18, 2016·Expert Opinion on Investigational Drugs·Kunal NepaliJing-Ping Liou
May 18, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maja J A de JongeJaap Verweij

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