Amifostine (Ethyoltrade mark, Alza Pharmaceuticals) is an inorganic 
thiophosphate cytoprotective agent known chemically as ethanethiol, 2-[3- 
aminopropyl)amino]dihydrogen phosphate. It is a prodrug of free thiol (WR-1065) 
that may act as a scavenger of free radicals generated in tissues exposed to 
cytotoxic drugs and binds to reactive metabolites of such drugs. Amifostine was 
originally developed as a radioprotective agent in a classified nuclear warfare 
project. Following declassification of the project it was evaluated as a 
cytoprotective agent against toxicity of the alkylating drugs and cisplatin. 
Differences in the alkaline phosphatase concentration of normal versus tumour 
tissues can result in greater conversion of amifostine in normal tissues. Inside 
the cell, WR-1065 provides an alternative target to DNA and RNA for the reactive 
molecules of alkylating or platinum agents and acts as a potent scavenger of the 
oxygen free radicals induced by ionizing radiation and some chemotherapy agents. 
Preclinical animal studies have demonstrated that the administration of 
amifostine protects against a variety of chemotherapy-related toxicities 
including cisplatin-induced nephrotoxicity, cisplatin-induced neurotoxicity, 
cyclophosphamide- and bleomycin-induced pulmonary toxicity and the 
cytotoxicities (including cardiotoxicity) induced by doxorubicin and related 
chemotherapeutic agents. Amifostine has been shown to protect a variety of 
animal species from lethal doses of radiation. Amifostine gives haematological 
protection from cyclophosphamide, carboplatin, mitomycin C, fotemustine and 
radiotherapy; renal and peripheral nerve protection from cisplatin; mucosa, skin 
and salivary gland protection from radiotherapy. Multiple Phase I studies were 
carried out with amifostine in combination with chemotherapy for various 
neoplasms. Appropriate doses of amifostine were found to be 740 - 910 mg/m(2) in 
single-dose regimens and 340 mg/m(2) in multiple-dose regimens. In 
radioprotection, doses are generally 200 - 350 mg/m(2). For all these 
characteristics, amifostine has been recently approved and suggested in ASCO 
clinical practice guidelines as a radioprotector for head and neck cancer 
treatment and supportive agent during cisplatin-based chemotherapy, in lymphomas 
and solid tumours. Moreover, its spectrum of possible applications is enlarging. 
As data have been provided indicating that amifostine stimulates haematopoiesis, 
it has been employed with intriguing results in the treatment of myelodysplastic 
syndromes (MDS).