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Clinical Cancer Research Vol. 6, 3038-3045, August 2000
© 2000 American Association for Cancer Research

Clinical Trials

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 Status1

Marie-Christine Mormont, James Waterhouse, Pascal Bleuzen, Sylvie Giacchetti, Alain Jami, André Bogdan, Joseph Lellouch, Jean-Louis Misset, Yvan Touitou and Francis Lévi2

Laboratoire "Rythmes Biologiques et Chronothérapeutique," Université Paris XI and I.C.I.G., Hopital Paul Brousse, 94800 Villejuif, France [M-C. M., P. B., S. G., A. J., J-L. M., F. L.]; School of Human Sciences, Liverpool John Moores University, Liverpool L3 3AF, United Kingdom [J. W.]; Département de Biochimie Médicale, Hopital de la Pitié-Salpêtrière, 75013 Paris, France [A. B., Y. T.]; and INSERM U 472, 94800 Villejuif, France [J. L.]

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.




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