The circadian rest-activity rhythm, a potential safety pharmacology endpoint of cancer chemotherapy

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Abstract

The robustness of the circadian timing system (CTS) was correlated to quality of life and predicted for improved survival in cancer patients. However, chemotherapy disrupted the CTS according to dose and circadian timing in mice. A continuous and repeated measures longitudinal design was implemented here to characterize CTS dynamics in patients receiving a fixed circadian-based chemotherapy protocol. The rest-activity rhythm of 49 patients with advanced cancer was monitored using a wrist actigraph for 13 days split into four consecutive spans of 3–4 days each,i.e., before, during, right after and late after a fixed chronotherapy course. The relative amount of activity in bedvs. out of bed (IWhat's new?

The health of the human circadian timing system is a factor in quality of life and survival among cancer patients. However, experimental evidence in animals suggests that chemotherapeutic agents may disrupt circadian rhythms. Here, rest-activity monitoring in patients receiving chemotherapy, which allowed for the precise characterization of chemotherapy-induced circadian disruption, shows that circadian disruption can be lacking, transient, or sustained, based on individual patients. Circadian monitoring provides early signals for guiding adjustment of dose and timing of chemotherapy, which could minimize adverse events and eventually maximize survival.

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