Weight loss and malnutrition are common symptoms of esophageal cancer, which can lead to skeletal muscle wasting and loss of adipose tissue. It was hypothesized before that the pharmacokinetics (PK) of chemotherapy may depend on body composition (Prado et al, 2013). In addition, we earlier showed that the clearance (CL; L/h) of unbound paclitaxel (pac) is related to body-surface area (BSA; m2) and gender (Bins et al, 2014). Therefore, now we aimed to assess the relationship between pac CL and body composition.
We analyzed 197 patients with stage III esophageal cancer who were treated with pac and carboplatin in a prospective study between 2008 and 2013. CL of pac, which was estimated using nonlinear mixed effects modeling (NONMEM) was used as a measure of systemic pac exposure (de Graan et al, 2012). Skeletal muscle index (SMI, cm2/m2), muscle attenuation (MA) and visceral adipose tissue (VAT; cm2) were measured at the level of the 3rd lumbar vertebra on computed tomography (CT) scans performed before treatment. Gender-specific differences in pac CL, based on the 1st quartile and the 4th quartile of the SMI and VAT measurement were analyzed with a Mann-Whitney test. A Spearman rank correlation (r) was calculated to explore the relationship between pac CL and SMI, VAT and MA, respectively.
CT images and pac PK data were available for 183 patients (78% was men). Pac CL was correlated with SMI (r = .27, p = .001) and VAT (r = .28, p = .001), while no correlation was found with MA (r < .01, p = .91). Interestingly, while in male patients with the highest SMI a higher pac CL was found compared to the lowest SMI (p = .024), and also for the 1st and 4th quartile of VAT (p = .003), in female patients no effect of SMI and VAT on pac CL was seen.
Skeletal muscle mass and visceral adipose tissue are positively correlated with pac CL in male patients with esophageal cancer. Differences in body composition between men and women may potentially explain the difference in the outcome of this analysis, and may also partly explain the difference in pac CL between both genders. Although the effect sizes are too small to support dose adaptions based on VAT or SMI, these parameters partly explain the large interpatient variability in pac PK.
Clinical trial identification
Legal entity responsible for the study
Erasmus MC Cancer Institute
All authors have declared no conflicts of interest.