Clinical and preclinical modulation of chemotherapy-induced toxicity in patients with cancer

Abstract

Anticancer treatment is generally associated with toxicity to health issues. One of the reasons for this unpleasant association is that anticancer agents have been mostly selected on the basis of an empirically established toxicity towards cancer cell lines and rapidly growing tumours in animal models, and not on the basis of a sophisticated intervention in tumour-specific biology. This strategy of drug development unavoidably produces drugs with toxicity towards normal cells and tissues which also have a high cell turnover and share many characteristics with tumour cells. Therefore it is a continuing challenge to design therapy which is both effective and also has high specificity for the biology of cancer and/or is efficiently targeted to tumour tissue. This article describes the mechanisms of cytotoxicity of standard chemo- and radiotherapy and discussed the possibilities of currently available cytoprotective agents to reduce or prevent these toxicities. These agents should ideally be selective for normal cells versus cancer cells, be effective in reducing or preventing toxicity, have no negative impact on anticancer therapy and have minimal adverse effects. None of the agents described in this article fulfils these criteria completely and therefore we cannot recommend these agents for standard use in daily anticancer practice. Nevertheless, there are encouraging data concerning the beneficial effects of dexrazoxane for anthracycline-induced cardiomyopathy and amifostine for platinum- and radiotherapy-induced toxicity. These date warrant further studies.