TY - JOUR
T1 - The influence of body composition on the systemic exposure of paclitaxel in esophageal cancer patients
AU - van Doorn, Leni
AU - Crombag, Marie Rose B.S.
AU - Rier, Hánah N.
AU - van Vugt, Jeroen L.A.
AU - van Kesteren, Charlotte
AU - Bins, Sander
AU - Mathijssen, Ron H.J.
AU - Levin, Mark David
AU - Koolen, Stijn L.W.
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/1/9
Y1 - 2021/1/9
N2 - 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/m2 . Median BSA was 1.98 m2 (range of 1.4 to 2.8 m2 ). 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.
AB - 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/m2 . Median BSA was 1.98 m2 (range of 1.4 to 2.8 m2 ). 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.
UR - http://www.scopus.com/inward/record.url?scp=85099353693&partnerID=8YFLogxK
U2 - 10.3390/ph14010047
DO - 10.3390/ph14010047
M3 - Article
C2 - 33435449
SN - 1424-8247
VL - 14
SP - 1
EP - 9
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 1
M1 - 47
ER -
