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

Zeinab Daher-Abdi 1, 2 Sandrine Lavau-Denes 3 Aurélie Prémaud 1, 2 Saik Urien 4 François-Ludovic Sauvage 1, 5 Jean Martin 3 Sophie Leobon 3 Pierre Marquet 1, 2, 5 Nicole Tubiana-Mathieu 3 Annick Rousseau 1, 2, *
* Auteur correspondant
1 PIST - Pharmacologie des Immunosuppresseurs et de la Transplantation
2 UNILIM - Université de Limoges
3 Service d'Oncologie médicale [CHU Limoges]
4 Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant
5 Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges]
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.
Keywords : capecitabine elderly pharmacokinetics response
Type de document :
Article dans une revue
Cancer Chemotherapy and Pharmacology, Springer Verlag, 2014, 73 (6), pp.1285-93. 〈10.1007/s00280-014-2466-0〉
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Soumis le : jeudi 10 avril 2014 - 15:56:57
Dernière modification le : vendredi 16 février 2018 - 15:25:04

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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, Springer Verlag, 2014, 73 (6), pp.1285-93. 〈10.1007/s00280-014-2466-0〉. 〈inserm-00976966〉

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