Cancer chronotherapy: is there a right time in the day to treat?

Cicadian variation in drug metabolism and tissue sensitivity to drugs impacts their activity and toxicity. A growing body of data suggests that therapy may be improved and toxicity reduced, by administering antineoplastic agents at carefully selected times of the day. This article gives background information that supports the predictable and exploitable nonlinear dynamic relationship between dose and effect that occurs each day, explores the ways in which clinical research must determine when to treat, wrestles with the question of the stability of circadian time structure in chronically ill cancer patients, and discusses the implications of the principles outlined to anticancer drug development.