Future development of amifostine as a radioprotectant.

Animal data and clinical trials document the efficacy of amifostine (WR-2721, Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) in decreasing the effects of radiation on normal tissues without decreasing the cytotoxic effects on malignant tumors. The selection of the optimal dose may depend on the intensity of the regimen to be administered as well as on the normal tissues to be protected. Also of important consideration is the question of how to sequence amifostine infusion. The optimal amifostine schedule during the course of the combined-modality treatment may require shortening the duration of chemotherapy infusion or giving amifostine in two split doses (before and after chemotherapy). Wide application of amifostine in once-daily/multiple-daily fractionated radiotherapy regimens may be facilitated by the availability of other, nonintravenous delivery routes, which are being explored. Although efforts are currently directed at amifostine-mediated modification of acute or late mucosal reactions associated with radiation therapy, there are many other radiation-induced toxicities. Further randomized studies are necessary to document the effects of amifostine on nonmucosal damage. Amifostine has the potential to protect a broad range of normal tissues from the toxicities of radiation and from certain forms of chemotherapy.