Abstract
BackgroundAdequate circadian timing of cancer treatment schedules (chronotherapy) can enhance tolerance and efficacy several-fold in experimental and clinical situations. However, the optimal timing varies according to sex, genetic background and lifestyle. Here, we compute the individual phase of the Circadian Timing System to decipher the internal timing of each patient and find the optimal treatment timing.MethodsTwenty-four patients (11 male; 13 female), aged 36 to 77 years, with advanced or metastatic gastro-intestinal cancer were recruited. Inner wrist surface Temperature, arm Activity and Position (TAP) were recorded every 10 min for 12 days, divided into three 4-day spans before, during and after a course of a set chronotherapy schedule. Pertinent indexes, I < O and a new biomarker, DI (degree of temporal internal order maintenance), were computed for each patient and period.ResultsThree circadian rhythms and the TAP rhythm grew less stable and more fragmented in response to treatment. Furthermore, large inter- and intra-individual changes were found for T, A, P and TAP patterns, with phase differences of up to 12 hours among patients. A moderate perturbation of temporal internal order was observed, but the administration of fixed chronomodulated chemotherapy partially resynchronized temperature and activity rhythms by the end of the study.ConclusionsThe integrated variable TAP, together with the asynchrony among rhythms revealed by the new biomarker DI, would help in the personalization of cancer chronotherapy, taking into account individual circadian phase markers.
Highlights
Adequate circadian timing of cancer treatment schedules can enhance tolerance and efficacy several-fold in experimental and clinical situations
This study has shown for the first time that in cancer patients the circadian system presents a huge variability in terms of phase distribution (12 hour spread among different patients) (Fig. 3) and more importantly, a moderately perturbed temporal internal order (Fig. 4)
These chronoenhancement techniques could potentially be useful to strengthen and synchronize cancer patients’ circadian system prior to chemotherapy administration, especially for those patients with persistent circadian disruption. This methodology would hypothetically, on the one hand, find the optimal time for their treatment and on the other hand, maximize treatment efficacy once administered at the right individual time. In summary, both experimental and clinical data support the relevance of a robust circadian system in order to enhance the efficacy and tolerability of chronomodulated treatments
Summary
Adequate circadian timing of cancer treatment schedules (chronotherapy) can enhance tolerance and efficacy several-fold in experimental and clinical situations. The optimal timing varies according to sex, genetic background and lifestyle. We compute the individual phase of the Circadian Timing System to decipher the internal timing of each patient and find the optimal treatment timing. Circadian disruption has been reported to decrease survival of Knowledge of the rhythmic features of drug metabolism, cellular detoxification and cell division cycle [7] has been used to optimize cancer treatments by means of chronotherapy. Chronotherapy mainly involves chronomodulated delivery schedules, and consists of the administration of each drug according to a delivery pattern with precise circadian times in order to achieve the best tolerance and efficacy [8]. Simpler approaches delivering a conventional treatment either during the morning or during the afternoon have been reported [9, 10].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
