Pharmacokinetics and exposure-effect relationships of capecitabine in elderly patients with breast or colorectal cancer. - Archive ouverte HAL Access content directly
Journal Articles Cancer Chemotherapy and Pharmacology Year : 2014

Pharmacokinetics and exposure-effect relationships of capecitabine in elderly patients with breast or colorectal cancer.

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Abstract

PURPOSE: The aims of the present study were (1) to investigate the impact of great age on pharmacokinetics of capecitabine and its metabolites and (2) to evaluate the exposure-effect relationship of capecitabine in elderly patients. METHODS: Data collected from 20 elderly patients (75-92 years old) with breast or colorectal cancer who received oral capecitabine were analyzed. In order to study the old age effect on pharmacokinetics, data collected from two phase I studies involving 40 younger adults (<75 years old) with metastatic cancer who received oral capecitabine were added in the database. The population pharmacokinetic analysis was based on a four-compartment model describing the sequence of capecitabine and three of its metabolites. RESULTS: The absorption rate constant was found lower in the oldest patient group (≥75 years) compared with the youngest group, and the constant rate elimination of the 5-fluorouracil metabolite was found decreased over time (i.e., after 2 consecutive weeks of capecitabine administration). This time effect was not found different between the two age groups. In elderly patients, the exposure-safety analysis showed, from the second cycle of chemotherapy, significantly higher median exposures of capecitabine and its metabolites (5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine and 5-fluorouracil) in patients who experienced hand-foot syndrome compared with patients who did not. CONCLUSION: This study puts forward new arguments for the treatment of elderly cancer patients who could benefit from capecitabine chemotherapy with acceptable toxicity.
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inserm-00976966 , version 1 (10-04-2014)

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Zeinab Daher-Abdi, Sandrine Lavau-Denes, Aurélie Prémaud, Saik Urien, François-Ludovic Sauvage, et al.. Pharmacokinetics and exposure-effect relationships of capecitabine in elderly patients with breast or colorectal cancer.: Population pharmacokinetics of capecitabine in elderly. Cancer Chemotherapy and Pharmacology, 2014, 73 (6), pp.1285-93. ⟨10.1007/s00280-014-2466-0⟩. ⟨inserm-00976966⟩
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