Cytoprotection: concepts and challenges.

Clinical trials with several toxicity protectors (cytoprotective or chemoprotective agents) have been performed during the past decade. These trials are quite complex since they must include sufficient dose-limiting events for study, and assessment of both toxicity (and therefore the efficacy of protection) and antitumor effects must be carried out. However, it is inevitable that with greater understanding of drug actions, one seeks to manipulate these for greater antitumor activity (biochemical modulation) or for lesser dose-limiting toxicity (cytoprotection) or for both. Examples of cytoprotective agents include dexrazoxane (ICRF-187), protecting against doxorubicin cardiotoxicity, and amifostine protecting against the myelosuppression of platinum and alkylating agents. In spite of the challenges encountered in the clinical development of these drugs, studies of cytoprotectors have led to a considerable understanding of important therapeutic issues and tangible clinical benefit in specific clinical situations.