ArticleCancer medicine2021
Worse capecitabine treatment outcome in patients with a low skeletal muscle mass is not explained by altered pharmacokinetics.
Article in Cancer medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Chemotherapy-Induced Changes in Plasma Amino Acids and Lipid Oxidation of Resected Patients with Colorectal Cancer: A Background for Future Studies.International journal of molecular sciences · 2024Article
- Article
- Pharmacokinetics of cancer therapeutics and energy balance: the role of diet intake, energy expenditure, and body composition.Journal of the National Cancer Institute. Monographs · 2023Review
- Influence of the skeletal muscle index on pharmacokinetics and toxicity of fluorouracil.Cancer medicine · 2023Article
- In vitro co-culture systems of hepatic and intestinal cells for cellular pharmacokinetic and pharmacodynamic studies of capecitabine against colorectal cancer.Cancer cell international · 2023Article
- The association between skeletal muscle measures and chemotherapy-induced toxicity in non-small cell lung cancer patients.Journal of cachexia, sarcopenia and muscle · 2022Article
- Worse capecitabine treatment outcome in patients with a low skeletal muscle mass is not explained by altered pharmacokinetics.Cancer medicine · 2021Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA low skeletal muscle mass (SMM) has been associated with increased toxicity and shorter survival in cancer patients treated with capecitabine, an oral prodrug of 5-fluorouracil (5-FU). Capecitabine and its metabolites are highly water-soluble and, therefore, more likely to distribute to lean tissues. The pharmacokinetics (PK) in patients with a low SMM could be changed, for example, by reaching higher maximum plasma concentrations. In this study, we aimed to examine whether the association between a low SMM and increased toxicity and shorter survival could be explained by altered PK of capecitabine and its metabolites.
methodsPreviously, a population PK model of capecitabine and metabolites in patients with solid tumors was developed. In our analysis, we included patients from this previous analysis for which evaluable abdominal computed tomography (CT)-scans were available. SMM was measured on CT-scans, by single slice evaluation at the third lumbar vertebra, using the Slice-o-Matic software. The previously developed population PK model was extended with SMM as a covariate, to assess the association between SMM and capecitabine and metabolite PK.
resultsPK and SMM data were available from 151 cancer patients with solid tumors. From the included patients, 55% had a low SMM. No relevant relationships were found between SMM and the PK parameters of capecitabine and, the active and toxic metabolite, 5-FU. SMM only correlated with the PK of the, most hydrophilic, but inactive and non-toxic, metabolite α-fluoro-β-alanine (FBAL). Patients with a low SMM had a smaller apparent volume of distribution and lower apparent clearance of FBAL.
conclusionsNo alterations in PK of capecitabine and the active and toxic metabolite 5-FU were observed in patients with a low SMM. Therefore, the previously identified increased toxicity and shorter survival in patients with a low SMM, could not be explained by changes in pharmacokinetic characteristics of capecitabine and metabolites.
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