Marked 24-h rest/activity rhythms are associated with better quality of life, better response, and longer survival in patients with metastatic colorectal cancer and good performance status.
The rest/activity circadian cycle has been used as a reference for chemotherapy administration at specific times to improve tolerability and efficacy. Because cancer processes may be associated with alterations of circadian rhythms, the rest/activity cycle was monitored noninvasively to assess its relationship with tumor response, survival, and quality of life in 200 patients with metastatic colorectal cancer. Patients wore an actigraph, a wristwatch that records the number of accelerations per minute, for 3 days before receiving chronomodulated chemotherapy. The circadian rhythms in activity were estimated by two robust parameters: the autocorrelation coefficient at 24 h (r24), and the dichotomy index (I<O) for comparing amounts of activity when in bed and out of bed. Accurate data for inclusion, quality of life, response, and survival were available for 192 patients. Survival at 2 years was 5-fold higher (P = 10(-4)) in patients with marked activity rhythm (I<O in upper quartile) than in those with rhythm alteration (I<O in lower quartile). These results were supported by the multivariate Cox analysis. Multivariate regression analysis showed that circadian rhythms in activity (I<O; P = 3 x 10(-4)) and in WBCs (P = 0.03) as well as performance status (P = 0.02) were jointly prognostic of response. Patients with marked rest/activity rhythms also had better quality of life and reported significantly less fatigue. The individual rest/activity cycle provides a novel independent prognostic factor for cancer patients' survival and tumor response as well as a quantitative indicator for quality of life.
Mormont
M C
MC
Laboratoire Rythmes Biologiques et Chronothérapeutique, Université Paris XI and I.C.I.G., Hopital Paul Brousse, Villejuif, France.
Waterhouse
J
J
Bleuzen
P
P
Giacchetti
S
S
Jami
A
A
Bogdan
A
A
Lellouch
J
J
Misset
J L
JL
Touitou
Y
Y
Lévi
F
F
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002940:Circadian Rhythm / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D004334:Drug Administration Schedule; D005221:Fatigue / Q000503:physiopathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D012720:Severity of Illness Index; D012893:Sleep Wake Disorders / Q000503:physiopathology; D016019:Survival Analysis; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil; D006854:Hydrocortisone