Originally developed against the effects of ionizing radiations, amifostine is 
an organic thiophosphate compound shown able to selectively protect normal 
tissues against cytotoxic agents in cellular and animal models, without 
protecting tumor tissues. Amifostine is a prodrug which is dephosphorylated into 
its active metabolite, a free thiol derivative, by membrane alkaline phosphatase 
of the target issue. This unique metabolism supports its cellular selectivity 
and its preferential uptake by normal tissues. In phase II clinical trials, a 
decreased toxicity has been demonstrated in patients given alkylating agents; 
however, reduction of the response has not been observed. On the basis of these 
results, a prospective, randomized, phase III study has been conducted in 
patients with ovarian carcinoma receiving a combination of cisplatinum and 
cyclophosphamide. A significant decrease in hematologic, renal and neurologic 
toxicity was observed in the amifostine-treated patients compared with the 
control group, and response rates did not significantly differ between the two 
groups. Insufficient or emerging data are only available for other applications, 
including either in vitro manipulation of hematopoietic grafts or in vivo 
treatment of non-Hodgkin's lymphoma, head and neck carcinoma, non-small cell 
lung cancer and radioprotection. No data are yet available in regard to the 
potential protective effects of amifostine against mutagenicity and 
cancerogenicity of both chemo- and radiotherapy.