Amifostine (WR-2721, Ethyol), S-2[3-aminopropylamino]-ethyl-phosphorothioic 
acid, was selected as a clinically usable radioprotector from more than 4,400 
compounds in the 1950s. A considerable amount of preclinical work suggested that 
amifostine, or its activated thiol WR-1065, protected normal cells effectively 
against the adverse effects of irradiation and several anticancer drugs without 
exhibiting tumor protection. In non-randomized and randomized trials in 
malignant melanoma, colorectal cancer, head and neck cancer, non-small cell lung 
cancer, and epithelial ovarian carcinoma, amifostine significantly reduced the 
hematological and non-hematological toxicity of DNA-damaging agents such as 
alkylators, platinum compounds, or mitomycin C. In more recent studies, the drug 
also protected patients from side effects produced by taxanes or topoisomerase I 
inhibitors and is thus likely to allow higher cytostatic doses to be 
administered. Currently, there is no evidence that amifostine compromises the 
antineoplastic effect of the drugs studied. Otherwise, W/R-2721 may even improve 
the therapeutic efficacy of agents like cisplatin, carboplatin, or paclitaxel. 
Moreover, amifostine appears to produce growth-factor like properties resulting 
in growth-promoting effects on primitive blood progenitor cells ex vivo. 
Amifostine offers a rational approach to protect patients against 
chemotherapy-specific and often dose-limiting effects and is thus likely to 
improve therapeutic outcome significantly. Future studies should be focused on 
both new indications like childhood cancer, myelodysplastic syndromes, 
dose-intensified or high- dose chemotherapy, and multimodality approaches and 
optimization of amifostine dosage in order to reduce dose-limiting side effects. 
Then, the drug may play a major role in more specific and individualized 
oncologic strategies.