Future development of amifostine in cancer treatment

Amifostine selectively protects normal, but not tumor, tissue from the cytotoxic damage induced by radiation therapy and chemotherapy. In a broad range of preclinical and phase II and III clinical studies, amifostine has been shown to substantially reduce anticancer drug-induced neutropenia, thrombocytopenia, nephrotoxicity, neurotoxicity (including ototoxicity and peripheral neuropathy), musculoskeletal toxicity, cardiotoxicity, and mutagenicity. Based on the rapidly expanding clinical trials database, there is strong rationale to design phase II and III studies of amifostine as a cytoprotective agent in patients with early and/or advanced breast, bladder, cervix, head and neck, small cell and non-small cell lung, ovarian, and rectal cancers, as well as melanoma, pediatric sarcomas, and lymphomas, including Hodgkin's disease. In this article, we have attempted to survey recently completed and ongoing phase II and III clinical studies and suggest specific designs for future clinical trials to establish the ultimate role of amifostine as a broad-spectrum cytoprotective agent.