Journal
PHARMACEUTICALS
Volume 14, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/ph14010047
Keywords
body composition; paclitaxel pharmacokinetics; esophageal cancer
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A study on patients with esophageal cancer found that changes in body composition do not predict paclitaxel pharmacokinetics well, and the impact of skeletal muscle index, visceral adipose tissue, and skeletal muscle density on predicting paclitaxel pharmacokinetics was also minimal.
Changes in body composition are associated with chemotherapy-related toxicities and effectiveness of treatment. It is hypothesized that the pharmacokinetics (PK) of chemotherapeutics may depend on body composition. The effects of body composition on the variability of paclitaxel PK were studied in patients with esophageal cancer. Skeletal muscle index (SMI), visceral adipose tissue (VAT), and skeletal muscle density (SMD) were measured at the third lumbar vertebra on computed tomography (CT) scans performed before treatment. Paclitaxel PK data were collected from a prospective study performed between May 2004 and January 2014. Non-linear mixed-effects modeling was used to fit paclitaxel PK profiles and evaluate the covariates body surface area (BSA), SMI, VAT, and SMD using a significance threshold of p < 0.001. Paclitaxel was administered to 184 patients in a dose range of 50 to 175 mg/m(2). Median BSA was 1.98 m(2) (range of 1.4 to 2.8 m(2)). SMI, VAT, and SMD were not superior to BSA in predicting paclitaxel PK. The additive value of SMI, VAT, and SMD to BSA was also negligible. We did not find evidence that paclitaxel dosing could be further optimized by correcting for SMI, VAT, or SMD.
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