The circadian rest‐activity rhythm,a potential safety pharmacology endpoint of cancer chemotherapy |
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| Authors: | Elisabet Ortiz‐Tudela Ida Iurisci Jacques Beau Abdoulaye Karaboue Thierry Moreau Maria Angeles Rol Juan Antonio Madrid Francis Lévi Pasquale F. Innominato |
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| Affiliation: | 1. Department of Physiology Chronobiology Laboratory, University of Murcia, Murcia, Spain;2. INSERM, UMRS776, Biological Rhythms and Cancers, Villejuif, France;3. Curie Institute, Rene Huguenin Hospital, Saint Cloud, France;4. Paris South University, Orsay, France;5. Department of Oncology APHP Chronotherapy Unit, Paul Brousse Hospital, Villejuif, France;6. INSERM, CESP Centre for Research in Epidemiology and Population Health, U 1018, Biostatistical Team, Villejuif, France;7. Paris South University, UMRS 1018, Villejuif, France |
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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 bed vs. out of bed (Ip < 0.05). Mean parameter values subsequently recovered to near baseline values. The occurrence of circadian disruption on chemotherapy was associated with a higher risk of clinically relevant fatigue (p = 0.028) or body weight loss (p = 0.05). Four CTS dynamic patterns characterized treatment response including no change (9.5% of the patients); improvement (14.3%); alteration and complete recovery (31%) or sustained deterioration (45%), possibly due to inadequate chronotherapy dosing and/or timing. Improved clinical tolerability could result from the minimization of circadian disruption through the personalization of chronotherapy delivery. |
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| Keywords: | rest‐activity rhythm actigraphy cancer chemotherapy circadian disruption toxicity |
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