The mechanism of action, pharmacokinetics, clinical efficacy, adverse effects, 
and dosage and administration of amifostine are reviewed. Amifostine is a 
prodrug converted by alkaline phosphatase to the active sulfhydryl compound 
WR-1065. WR-1065 protects normal cells by scavenging free radicals, donating 
hydrogen ions to free radicals, depleting oxygen, and binding to active 
derivatives of antineoplastic agents. The immediate conversion of amifostine to 
WR-1065, its small volume of distribution, and the limited amount of drug and 
metabolite recovered in the urine suggest that amifostine is rapidly 
dephosphorylated and enters cells as its active metabolite. The selectivity of 
amifostine for normal tissue is hypothesized to be a results of the decreased 
vascularity of tumors, decreased activity of alkaline phosphatase in tumor 
cells, and pH dependence of WR-1065 uptake. In clinical studies, amifostine 
decreased the frequency of cisplatin-induced nephrotoxicity, ototoxicity, 
neurotoxicity, and myelosuppression. Amifostine has demonstrated an ability to 
decrease the hematologic toxicity of cyclophosphamide, carboplatin, mitomycin, 
and antineoplastic drug combinations. Amifostine has FDA-approved labeling for 
use in reducing cumulative renal toxicity in patients receiving repeat doses of 
cisplatin for advanced ovarian cancer and non-small-cell lung cancer. The 
recommended dose in adults is 910 mg/m2 administered as a 15-minute infusion 30 
minutes before the start of chemotherapy. The major adverse effects of 
amifostine include hypotension and emesis. The benefits of amifostine must be 
weighted against its potential adverse effects, and the drug's impact on the 
efficacy of antineoplastics should be further investigated. Amifostine has shown 
promise in protecting non-malignant cells from the toxic effects of 
antineoplastics, apparently without compromising toxicity against cancer cells.