Neurologic protection by amifostine

Abstract

Amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) is a thiophosphate cytoprotectant agent with the potential to abrogate many chemotherapy-induced toxicities. In preclinical studies, amifostine protected against the cytotoxic effects of alkylating agents, platinum analogs, and radiation therapy in normal tissues, but preserved antineoplastic activity of these therapeutic modalities in tumor tissue. Most normal tissues were protected, including bone marrow, kidney, lung, and peripheral nerves. Recently, the protective effects of amifostine were confirmed by clinical studies, including a randomized trial demonstrating protection from cisplatin-induced myelosuppression, nephrotoxicity, and neurotoxicity. Many common chemotherapeutic agents, such as cisplatin, paclitaxel, and vinca alkaloids, cause dose-limiting neurotoxicity. Therefore, a neurologic protectant may help to reduce toxicity to patients, improve the tolerability of combination therapy with multiple neurotoxic agents, or allow investigators to intensify chemotherapy dose. This report reviews the potential role of amifostine as a neuroprotectant. Future clinical trials may expand the use of amifostine to abrogate neurotoxicity from multiple agents and combinations and compare amifostine with other neuroprotective agents.