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 chemotherapy-induced cellular injury through free-radical scavenging, hydrogen donation, and inhibition of DNA damage. Amifostine is metabolised and accumulated to a much greater extent in normal cells than in tumour 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 have shown that amifostine protects against radiation damage and against the myelotoxic, nephrotoxic and neurotoxic effects of chemotherapeutic agents such as alkylating agents and platinum compounds. In some cases, the antitumour effects of these agents have been potentiated by amifostine. Amifostine has also been shown to protect against radiation- and chemotherapy-induced mutagenesis and, as a result, carcinogenesis. Use of amifostine allows for safer and more effective administration of radio- and anticancer therapy.
Peters
G J
GJ
Biochemical Pharmacology Section, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
van der Vijgh
W J
WJ
D004999:Amifostine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D007036:Hypothermia, Induced; D016296:Mutagenesis / Q000187:drug effects; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011837:Radiation-Protective Agents; D004999:Amifostine