Influence of age on pharmacokinetics of capecitabine and its metabolites in older adults with cancer: a pilot study
Files
(Published version)
Date
2023
Authors
Shafiei, M.
Galettis, P.
Beale, P.
Reuter, S.E.
Martin, J.H.
McLachlan, A.J.
Blinman, P.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Cancer Chemotherapy and Pharmacology, 2023; 92(2):135-139
Statement of Responsibility
Conference Name
Abstract
Background: Capecitabine is an oral chemotherapy prodrug of 5-fluorouracil (5-FU) with unpredictable toxicity, especially in older adults. The aim of this study was to evaluate the pharmacokinetics (PK) of capecitabine and its metabolites in younger adults (< 70 years) and older adults (≥ 70 years) receiving capecitabine for solid cancer.
Methods: Eligible participants receiving capecitabine had 2 venous samples collected on day 14 of cycle 1 and cycle 2 of their treatment. Capecitabine and metabolite concentrations were determined using liquid chromatography with tandem mass spectrometry. A Bayesian estimation approach was used to generate individual estimates of PK parameters for 5-FU. A linear mixed-effect analysis of variance (ANOVA) model was used to compare dose-normalised log-transformed PK parameters between age groups. Correlations were determined by linear regression and logistic regression analyses.
Results: Of the total 26 participants, 58% were male with a median age of 67 years (range, 37–85) with 54% aged < 70 years and 46% aged ≥ 70 years. Participants aged ≥ 70 years, compared to those aged < 70 years, had a greater 5-FU exposure based on area under the concentration–time curve (AUC) of 17% (90% CI 103–134%; 0.893 vs. 0.762 mg h/L) and 14% increase in maximal concentration, Cmax (90% CI 82.1–159%; 0.343 vs. 0.300 mg/L). The 5-FU Cmax was positively associated with time up and go (TUG) (Pearson’s correlation 0.77, p = 0.01), but not other geriatric assessment domains or severe toxicity.
Conclusion: 5-FU exposure was significantly increased in older adults compared to younger adults receiving equivalent doses of capecitabine, and is a possible cause for increased toxicity in older adults.
School/Discipline
Dissertation Note
Provenance
Description
Data source: Supplementary information, https://doi.org/10.1007/s00280-023-04552-5
Access Status
Rights
Copyright Crown 2023
Access Condition Notes: Accepted manuscript available after 1 July 2024