Giacchetti, S., Dugue, P. A., Innominato, P. F., Bjarnason, G. A., Focan, C., Garufi, C., Tumolo, S., Coudert, B., Iacobelli, S., Smaaland, R., Tampellini, M., Adam, R., Moreau, T. and Lévi, Francis A. (2012) Sex moderates circadian chemotherapy effects on survival of patients with metastatic colorectal cancer : a meta-analysis. Annals of Oncology, Volume 23 (Number 12). pp. 3110-3116. doi:10.1093/annonc/mds148 ISSN 0923-7534.

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Abstract

BACKGROUND:
Molecular circadian clocks can modify cancer chemotherapy effects, with a possible moderation according to sex differences. We investigated whether sex determine the optimal delivery schedule of chemotherapy for metastatic colorectal cancer.
PATIENTS AND METHODS:
A meta-analysis was performed using individual data from three international Phase III trials comparing 5-fluorouracil, leucovorin and oxaliplatin administered in chronomodulated (chronoFLO) or conventional (CONV) infusions. The data from 345 females and 497 males were updated at 9 years. The main end point was survival.
RESULTS:
Overall survival was improved in males on chronoFLO when compared with CONV (P = 0.009), with respective median values of 20.8 (95% CL, 18.7 to 22.9) and 17.5 months (16.1 to 18.8). Conversely, median survival was 16.6 months (13.9 to 19.3) on chronoFLO and 18.4 months (16.6 to 20.2) on CONV in females (P = 0.012). The sex versus schedule interaction was a strong predictive factor of optimal treatment schedule, with a hazard ratio of 1.59 (1.30 to 1.75) for overall survival (P = 0.002) in multivariate analysis.
CONCLUSIONS:
Males lived significantly longer on chronomodulated chemotherapy rather than on conventional chemotherapy. The current chronoFLO schedule deserves prospective assessment as a safe and more effective first-line treatment option than conventional delivery for male patients.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology R Medicine > RC Internal medicine
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Circadian rhythms, Cancer—Chemotherapy--Sex differences , Metastasis , Rectum--Cancer , Colon (Anatomy)--Cancer
Journal or Publication Title:	Annals of Oncology
Publisher:	Oxford University Press
ISSN:	0923-7534
Official Date:	December 2012
Dates:	Date Event December 2012 Published 27 June 2012 Available
Volume:	Volume 23
Number:	Number 12
Number of Pages:	7
Page Range:	pp. 3110-3116
DOI:	10.1093/annonc/mds148
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Funder:	Association pour la Recherche sur le Temps Biologique et la Chronothérapie (ARTBC International, Hôpital Universitaire Paul Brousse (Villejuif, France)

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