CIRCADIAN CANCER-THERAPY

Purpose and Design: To review briefly the growing body of published data about circadian variation in cytotoxic drug metabolism and tissue sensitivity to chemotherapeutic agents. The suggestion that toxicity may be reduced and anticancer efficacy improved by administering antineoplastic agents at carefully selected times of the day was assessed. Results and Conclusion: The medical literature describing molecular, cellular, and organismic time- keeping mechanisms, as well as circadian rhythms, in cytokinetic, pharmacokinetic, and pharmacodynamic parameters relevant to cancer chemotherapy, which support the predictable rhythmic relationship between dose and effect that occurs during each day, were reviewed. Advantages for optimal circadian scheduling have been demonstrated for diminishing side effects and increasing maximal safe dose-intensity of drugs of diverse class. The use of the predictable circadian relationship of dose and response provides another increment of progress in the treatment of cancer patients.