By chronomodulating 5-FU-LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.

The rest-activity circadian rhythm (CircAct) reflects the function of the circadian timing system. In a prior singleinstitution study, the extent of CircAct perturbation independently predicted for survival and tumor response in 192 patients receiving chemotherapy for metastatic colorectal cancer. Moreover, the main CircAct parameters correlated with several health-related quality of life (HRQoL) scales. In this prospective study, we attempted to extend these results to an independent cohort of chemotherapy-naive metastatic colorectal cancer patients participating in an international randomized phase III trial (European Organisation for Research and Treatment of Cancer 05963). Patients were randomized to receive chronomodulated or conventional infusion of 5-fluorouracil, leucovorin, and oxaliplatin as first-line treatment for metastatic colorectal cancer. Patients from nine institutions completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and wore a wrist accelerometer (actigraph) for 3 days before chemotherapy delivery. Two validated parameters (I |0.25|; P < 0.01). I

The respective roles of 1-OHP dose and schedule and circadian peak time of drug delivery are being investigated with regard to the high activity of this three-drug, chronomodulated chemotherapeutic regimen.

Both regimens achieved similar median survival times more than 18 months with an acceptable toxicity. The chronomodulated schedule produced a survival advantage over FOLFOX in men. The strong sex dependency of optimal scheduling of fluorouracil, leucovorin, and oxaliplatin calls for translational investigations of determinants related to the patient's molecular clock.

The incidence of cardiac end points remains low even after longer-term follow-up. The cumulative incidence of any type of cardiac end point increases during the scheduled treatment period of 1 year, but it remains relatively constant thereafter.

The clinical relevance of circadian rhythm modifications in patients on chemotherapy is unknown. Even so, circadian parameter I

No abstract

Wrist actimetry circadian rhythm as a robust predictor of colorectal cancer patients survival. Chronobiology International, 31 (8). pp. 891-900. Permanent WRAP URL:http://wrap.warwick.ac.uk/85076 Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-for profit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. A note on versions:The version presented here may differ from the published version or, version of record, if you wish to cite this item you are advised to consult the publisher's version. Please see the 'permanent WRAP URL' above for details on accessing the published version and note that access may require a subscription. Running titleRest-activity rhythm as a predictor of survival Key wordsBiomarkers, cancer, circadian clock, rest-activity rhythm, survival Interventional studies involving 24-h schedules of clock-targeted drugs, light intensity, exercise and/or meals are needed for testing the relevance of circadian synchronization for the survival of patients with disrupted rhythms.