Amifostine: is there evidence of tumor protection?

A large body of experimental evidence suggests that amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD) is a selective cytoprotector of normal tissues. Nevertheless, several experimental studies, most of which were conducted in the early 1980s, suggest that amifostine may protect tumor tissues, although to a much lower degree than its protective effect on normal tissues. Based on a critical literature review, we conclude that any experimental evidence suggesting tumor protection is weak. The effects of anesthesia and hypotension on normal and tumor tissue oxygenation status of animals, the consequences of such events on amifostine activity, and the impact of this complex situation on host immunity and radiotherapy efficacy in the experimental setting do not reliably simulate the clinical setting. Analyses of radiobiologic and histologic results of the Canine Sarcoma Study show that, if any conclusion is to be made, amifostine protected normal tissues and preserved (or even enhanced) the antitumor activity of radiotherapy. The Ormaplatin Study clearly showed a 10-fold decreased concentration of platinum in tumor compared with normal tissues, and does not therefore support evidence of lack of amifostine selectivity. Finally, not one clinical study suggests tumor protection with amifostine. On the contrary, the majority of clinical data strongly suggest that patients who receive amifostine with radiotherapy and/or chemotherapy do better than controls. Rather than organizing large-scale, randomized clinical trials to exclude tumor protection by amifostine, it seems more useful to design trials that would measure amifostine benefits in terms of improved quality of life, tumor control, and survival rates in patients being treated with standard or novel chemotherapy/radiotherapy regimens.