title: Marker rhythms of circadian system function: a study of patients with metastatic colorectal cancer and good performance status.
abstract: Cancer patients may exhibit normal or altered circadian rhythms in tumor and healthy tissues. Four rhythms known to reflect circadian clock function were studied in 18 patients with metastatic colorectal cancer and good performance status. Rest-activity was monitored by wrist actigraphy for 72 h before treatment, and its circadian rhythm was estimated by an autocorrelation coefficient at 24h and a dichotomy index that compared the activity level when in and out of bed. Blood samples (9-11 time points, 3-6 h apart) were drawn on day 1 and day 4 of the first course of chronochemotherapy (5-fluorouracil: 800 mg/m2/day; folinic acid: 300 mg/m2/day; oxaliplatin: 25 mg/m2/day). Group 24h rhythms were validated statistically for plasma concentrations of melatonin, 6-alpha-sulfatoxymelatonin, and cortisol and for lymphocyte counts. Significant individual 24h rhythms were displayed in melatonin by 15 patients, cortisol by seven patients, lymphocytes by five patients, and prominent circadian rhythms in activity were displayed by 10 patients; only one patient exhibited significant rhythms in all the variables. The results suggest the rhythms of melatonin, cortisol, lymphocytes, and rest/activity reflect different components of the circadian system, which may be altered differently during cancer processes. Such 24h rhythm alterations appeared to be independent of conventional clinical factors.
authors.affiliation: INSERM EPI 0118 Cancer Chronotherapeutics, Université Paris XI, Hĵpital Paul Brousse, Villejuif, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Mormont
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Langouët
authors.forename: Bruno
authors.initials: B
authors.lastname: Claustrat
authors.forename: André
authors.initials: A
authors.lastname: Bogdan
authors.forename: Sylvie
authors.initials: S
authors.lastname: Marion
authors.forename: Jim
authors.initials: J
authors.lastname: Waterhouse
authors.forename: Yvan
authors.initials: Y
authors.lastname: Touitou
authors.forename: Francis
authors.initials: F
authors.lastname: Lévi
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002940:Circadian Rhythm / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000097:blood / Q000503:physiopathology* / Q000556:secondary; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D017567:Karnofsky Performance Status; D018655:Lymphocyte Count; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000097:blood; D008875:Middle Aged; D009043:Motor Activity; D012463:Saliva / Q000378:metabolism
chemical_list: D015415:Biomarkers; C054513:6-sulfatoxymelatonin; D008550:Melatonin; D006854:Hydrocortisone