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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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Acknowledgments

The CAPAGEC study was funded by the Limoges University Hospital. We thank Fabrice Béavogui, Karine Bariller, Franck Giraudie and Jean Louis Dupuy for their technical assistance, and Karen for her complete English and grammatical review of this paper. Pierre Marquet has received research grants and honoraria from ROCHE.

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Authors and Affiliations

  1. UMR-S850, Faculty of Pharmacy, Inserm, 2 Rue Dr Marcland, 87025, Limoges Cedex, France

    Z. Daher Abdi, A. Prémaud, F. L. Sauvage, P. Marquet & A. Rousseau

  2. Laboratoire de Pharmacologie médicale, Univ Limoges, Limoges, France

    Z. Daher Abdi, A. Prémaud, P. Marquet & A. Rousseau

  3. CHU Limoges, Service oncologie médicale, Limoges, France

    S. Lavau-Denes, J. Martin, S. Leobon & N. Tubiana-Mathieu

  4. EA 3620, Univ Paris Descartes, Sorbonne Paris Cité, France

    S. Urien

  5. CHU Limoges, Service de pharmacologie, toxicologie et pharmacovigilance, Limoges, France

    F. L. Sauvage & P. Marquet

Authors
  1. Z. Daher Abdi
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  2. S. Lavau-Denes
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  3. A. Prémaud
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  4. S. Urien
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  5. F. L. Sauvage
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  6. J. Martin
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  7. S. Leobon
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  9. N. Tubiana-Mathieu
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  10. A. Rousseau
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Corresponding author

Correspondence to A. Rousseau.

Additional information

Z. Daher Abdi, S Lavau-Denes and A Prémaud equally contributed to this work as the second authors.

N Tubiana-Mathieu and A Rousseau equally contributed to this work as the last authors.

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Daher Abdi, Z., Lavau-Denes, S., Prémaud, A. et al. Pharmacokinetics and exposure–effect relationships of capecitabine in elderly patients with breast or colorectal cancer. Cancer Chemother Pharmacol 73, 1285–1293 (2014). https://doi.org/10.1007/s00280-014-2466-0

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  • DOI: https://doi.org/10.1007/s00280-014-2466-0

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