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

Anticancer treatment is generally associated with toxicity to health issues . One of the reasons for this unpleasant association is that anticancer age nts have been mostly selected on the basis of an empirically established to xicity towards cancer cell lines and rapidly growing tumours in animal mode ls, 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 turn over and share many characteristics with tumour cells. Therefore it is a co ntinuing challenge to design therapy which is both effective and also has h igh specificity for the biology of cancer and/or is efficiently targeted to tumour tissue. This article describes the mechanisms of cytotoxicity of standard chemo- an d radiotherapy and discussed the possibilities of currently available cytop rotective 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 the rapy and have minimal adverse effects. None of the agents described in this article fulfils these criteria completely and therefore we cannot recommen d these agents for standard use in daily anticancer practice. Nevertheless, there are encouraging data concerning the beneficial effects of dexrazoxan e for anthracycline-induced cardiomyopathy and amifostine for platinum- and radiotherapy-induced toxicity. These date warrant further studies.