Circadian timing in cancer treatment: the biological foundation for an integrative approach.

Despite the many innovations that have occurred in cancer treatment, the age-specific mortality for most adult tumors has remained stable during the past 30 years. There have been clinically significant improvements in the outcomes of young and middle-aged patients, yet the vast majority of cancer patients are more than 50 years of age, among whom we observe few improvements in clinical outcomes. Clearly, many of today's cytotoxic agents have been shown to be effective in-vitro and in animal model systems; however, few have proved efficacious in dramatically improving survival outcomes in adult cancer. There is now increasing evidence to suggest that the administration of cytotoxic agents, at the appropriate circadian phase, can significantly increase the therapeutic index of current cancer therapies.