CYTOPROTECTION - CONCEPTS AND CHALLENGES

Clinical trials with several toxicity protectors (cytoprotective or ch emoprotective agents) have been performed during the past decade. Thes e trials are quite complex since they must include sufficient dose-lim iting 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 ac tions, one seeks to manipulate these for greater antitumor activity (b iochemical modulation) or for lesser dose-limiting toxicity (cytoprote ction) or for both. Examples of cytoprotective agents include dexrazox ane (ICRF-187), protecting against doxorubicin cardiotoxicity, and ami fostine protecting against the myelosuppression of platinum and alkyla ting agents. In spite of the challenges encountered in the clinical de velopment of these drugs, studies of cytoprotectors have led to a cons iderable understanding of important therapeutic issues and tangible cl inical benefit in specific clinical situations.