Strategies for using cytoprotective agents to improve outcomes associated with cancer chemotherapy

During the past decade, advances in cancer treatment using multimodality therapy with complex and intensive chemotherapy regimens have resulted in the long-term survival of approximately 50% of the patients diagnosed with the disease. Although systemic chemotherapy is effective in extending and improving the lives of many patients with cancer, it may also induce acute and long-term cellular injury to normal cells leading to significant toxicity. Efforts utilizing cytoprotectants to avoid injury to normal cells may minimize toxicity, allow dose intensification, and improve the quality of life of patients receiving chemotherapy. A successful cellular cytoprotectant is an agent that protects normal cells from chemotherapy without abrogating the antitumor effects of chemotherapy. Recently, agents have been developed with specificity to protect normal cells without protecting tumor cells. The currently available cytoprotectants mesna, dexrazoxane, and amifostine are discussed in this review. The application of these agents is discussed and contrasted to the use of rescue agents, which are used to rescue cells after damage has already occurred. Understanding the usefulness of such agents will improve our ability to care for patients receiving chemotherapy while enhancing both the short- and long-term outcomes in this patient population.