presentation/295 1st BioSim Conference - Presentation

1st BioSim Conference


Gender, a determinant of toxicity and survival in cancer patients receiving circadian chronotherapy

Author: Francis Levi, INSERM U776 “Rythmes biologiques et cancers”, hôpital Paul Brousse, Villejuif.

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Oral or poster: Oral presentation

Interindividual variability represents a main cause for unpredictable pharmacokinetics, tolerability and efficacy of therapeutics, yet the tools to select the right drugs in the right dose and at the right time for an individual patient have not yet been validated. However, the delivery of cancer chemotherapy at a proper circadian time has improved tolerability and antitumor efficacy as compared to constant rate infusion in two randomised trials.
In two subsequent clinical trials involving a total of 668 patients with metastatic colorectal cancer, we have recently identified gender as a main determinant of tolerability and survival on chronomodulated chemotherapy (1, 2). Women experienced significantly more adverse events than men, despite same or lower dose intensities. This was true for several delivery schedules of the most active combination chemotherapy in this disease (5-fluorouracil-leucovorin-oxaliplatin). In addition, a 12 h shift in the peak time of drug delivery was responsible for a 5-fold increase in the occurrence of severe toxicity in men, while such circadian pattern was less predictable in women. Furthermore, the median survival of women receiving chronotherapy was 16 months as compared to 21 months for men (p<0.001). Gender-dependencies in drug polymorphism may to some extent account for these results. Yet a modelisation approach should help design novel experimental and clinical studies in order to confirm this ...
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1st BioSim Conference. October 6th to October 8th, 2005. Palma de Mallorca, Spain.