e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

Influence of age on pharmacokinetics of capecitabine and its metabolites in older adults with cancer: a prospective observational study (#203)

Mohsen Shafiei 1 2 , Peter Galettis 3 , Philip Beale 1 2 , Stephanie Reuter 4 , Jennifer Martin 3 , Andrew McLachlan 5 , Prunella Blinman 1 2
  1. Concord Clinical School, Faculty of Medicine and Health, University of Sydney, Concord, NSW, Australia
  2. Concord Hospital, Concord, NSW, Australia
  3. School of Medicine & Public Health, The University of Newcastle, Centre for Drug Repurposing and Medicines Research, Callaghan, NSW, Australia
  4. UniSA Clinical and Health Sciences, University of South Australia, Adelaide, , SA, Australia
  5. Sydney Pharmacy School, University of Sydney, Sydney, NSW, Australia

Background: Capecitabine is an oral chemotherapy used in the management of people with solid cancers. When based on conventional body surface area (BSA) dosing, capecitabine has unpredictable toxicity especially in older adults. This study aimed to evaluate the comparative pharmacokinetics (PK) of capecitabine and its metabolites in younger adults (<70 years) and older adults (≥70 years) receiving capecitabine for solid cancer and the correlation with chemotherapy-related toxicity and geriatric assessment tools.

Methods: Eligible participants receiving BSA-based capecitabine had two venous samples collected on the day 14 of cycle 1 and 2 of their treatment. Capecitabine and metabolite concentrations were determined using liquid chromatography with tandem mass spectrometry. A Bayesian estimation approach was used based on an existing population pharmacokinetic model to generate individual estimates of PK parameters. An ANOVA model was used to compare dose-normalised log-transformed PK parameters between age groups. Linear regression and logistic regression analysis were used to determine the correlation between capecitabine and metabolite PK and domains of geriatric assessment and toxicity respectively.   

Results: Of the total 26 participants (14 aged <70 years;12 aged ≥70 years), 15 were male and 11 were female. In the older age group, compared to the younger group, a 17% greater 5-fluorouracil (5-FU) exposure (AUCtau 0.91 vs 0.77mg.h/L, 90%CI:103–134%) and 14% increase in maximal concentrations (Cmax 0.37 vs 0.33mg/L, 90%CI:82.1–159%) were observed. Dose-normalised 5-FU Cmax was positively associated with the timed up and go test (Pearson correlation 0.57, p=0.02). Capecitabine and metabolite PK were not correlated with observed severe toxicity (p=0.34).

Conclusion: 5-FU exposure was significantly increased in older adults compared to younger adults when normalised for dose. Further investigation is required to determine the clinical significance of these results including whether it contributes to excess toxicity and/or provides a rationale for dose modifications in older adults.