PROTECTION OF NORMAL-TISSUES FROM THE CYTOTOXIC EFFECTS OF CHEMOTHERAPY AND RADIATION BY AMIFOSTINE (WR-2721) - PRECLINICAL ASPECTS

Amifostine is a radioprotective agent that prevents radiation- and che motherapy-induced cellular injury through free-radical scavenging, hyd rogen donation, and inhibition of DNA damage. Amifostine is metabolise d and accumulated to a much greater extent in normal cells than in tum our cells. As a result, it exerts a protective effect from toxicity on normal tissues induced by chemo- or radiotherapy without reducing the antitumour effects of cancer therapy. Extensive preclinical studies h ave shown that amifostine protects against radiation damage and agains t the myelotoxic, nephrotoxic and neurotoxic effects of chemotherapeut ic agents such as alkylating agents and platinum compounds. In some ca ses, the antitumour effects of these agents have been potentiated by a mifostine. Amifostine has also been shown to protect against radiation - and chemotherapy-induced mutagenesis and, as a result, carcinogenesi s. Use of amifostine allows for safer and more effective administratio n of radio and anticancer therapy.