Amifostine (Ethyol), an inorganic thiophosphate, is a selective broad-spectrum 
cytoprotector of normal tissues that provides cytoprotection against ionizing 
radiation and chemotherapeutic agents, thus preserving the efficacy of 
radiotherapy and chemotherapy. This review summarizes the preclinical data and 
clinical experience with amifostine, and provides insight into future clinical 
directions. Amifostine, an inactive pro-drug, is transformed to an active thiol 
after dephosphorylation by alkaline phosphatase found in the normal endothelium. 
The absence of alkaline phosphatase in the tumoral endothelium and stromal 
components, and the hypovascularity and acidity of the tumor environment, may 
explain its cytoprotective selectivity. The cytoprotective mechanism of 
amifostine is complicated, involving free radical scavenging, DNA protection and 
repair acceleration, and induction of cellular hypoxia. Intravenous 
administration of amifostine 740-900 mg/m(2) before chemotherapy and 250-350 
mg/m(2) before each radiotherapy fraction are widely used regimens. The US Food 
and Drug Administration has approved the use of amifostine as a cytoprotector 
for cisplatin chemotherapy and for radiation-induced xerostomia. Ongoing trials 
are being conducted to determine the efficacy of amifostine in reducing 
radiation-induced mucositis and other toxicities. Novel schedules and routes of 
administration are under investigation, and may further simplify the use of 
amifostine and considerably broaden its applications.