Original Article

Cancer Chemotherapy and Pharmacology

, Volume 73, Issue 6, pp 1285-1293

First online:

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

  • Z. Daher AbdiAffiliated withUMR-S850, Faculty of Pharmacy, InsermLaboratoire de Pharmacologie médicale, Univ Limoges
  • , S. Lavau-DenesAffiliated withCHU Limoges, Service oncologie médicale
  • , A. PrémaudAffiliated withUMR-S850, Faculty of Pharmacy, InsermLaboratoire de Pharmacologie médicale, Univ Limoges
  • , S. UrienAffiliated withEA 3620, Univ Paris Descartes
  • , F. L. SauvageAffiliated withUMR-S850, Faculty of Pharmacy, InsermCHU Limoges, Service de pharmacologie, toxicologie et pharmacovigilance
  • , J. MartinAffiliated withCHU Limoges, Service oncologie médicale
  • , S. LeobonAffiliated withCHU Limoges, Service oncologie médicale
  • , P. MarquetAffiliated withUMR-S850, Faculty of Pharmacy, InsermLaboratoire de Pharmacologie médicale, Univ LimogesCHU Limoges, Service de pharmacologie, toxicologie et pharmacovigilance
  • , N. Tubiana-MathieuAffiliated withCHU Limoges, Service oncologie médicale
    • , A. RousseauAffiliated withUMR-S850, Faculty of Pharmacy, InsermLaboratoire de Pharmacologie médicale, Univ Limoges Email author 

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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.

Keywords

Capecitabine Elderly Pharmacokinetics Response