Circadian-system alterations during cancer processes: a review.

Murine and human data have indicated that tumors and tumor-bearing hosts may exhibit nearly normal or markedly altered circadian rhythms. Amplitude damping, phase shifts, and/or period (tau) change, including appearance of ultradian rhythms (with tau < 20 hr) usually become more prominent at late stages of cancer development. The extent of rhythm alterations also varies according to tumor type, growth rate and level of differentiation. While "group chronotherapy," i.e., administration of the same chronomodulated schedule to cancer patients, has increased chemotherapy efficacy and/or tolerability, cancer patients' individual circadian rhythms now need to be explored on a large scale, in order to estimate the incidence of cancer-associated circadian-system alterations and to understand the underlying mechanisms. Correlations between such alterations and patient outcome must be established in order to specify the need for individualized chronomodulated delivery schedules and/or specific rhythm-oriented therapy, especially in patients with circadian-system disturbances.