The sulfhydryl containing compounds WR-2721 and glutathione as radio- and chemoprotective agents. A review, indications for use and prospects

Radio- and chemotherapy for the treatment of malignancies are often associa ted with significant toxicity. One approach to reduce the toxicity is the c oncomitant treatment with chemoprotective agents. This article reviews two sulfhydryl compounds, namely the agent WR-2721 (amifostine), a compound rec ently registered for use in human in many countries, and the natural occurr ing compound glutathione (GSH). GSH is not registered as a chemoprotective agent. WR-2721 is an aminothiol prodrug and has to be converted to the acti ve compound WR-1065 by membrane-bound alkaline phosphatase. WR-1065 and GSH both act as naturally occurring thiols. No protective effect on the tumour has been found when these compounds are administered intravenously. There is even in vitro evidence for an increased anti-tumour effect with mafosfam ide after pretreatment with WR-2721, and in vivo after treatment with carbo platin and paclitaxel. Randomized clinical studies have shown that WR-2721 and GSH decrease cisplatin-induced nephrotoxicity and that WR-2721 reduces radiation radiotherapy-induced toxicity. Side-effects associated with WR-27 21 are nausea, vomiting and hypotension, GSH has no side-effects. An exact role of WR-2721 and GSH as chemoprotectors is not yet completely clear. Fut ure studies should examine the protective effect of these drugs on mucositi s, cardiac toxicity, neuro- and ototoxicity, the development of secondary n eoplasms and their effect on quality of life.