Association of Body Composition with Outcome of Docetaxel Chemotherapy in Metastatic Prostate Cancer: A Retrospective Review

<div><p>Background</p><p>Docetaxel, a lipophilic drug, is indicated for castration-resistant metastatic prostate cancer. Most men with such disease would have had androgen-deprivation therapy, which decreases muscle and increases body fat. Obesity and body composition changes may influence the outcomes of docetaxel therapy.</p><p>Methods</p><p>We conducted a retrospective review of 333 patients with metastatic prostate cancer treated with docetaxel at a comprehensive cancer center between October 7, 2004 and December 31, 2012. Body composition parameters were measured based on the areas of muscle and adipose tissues in the visceral and subcutaneous compartments on CT images at L3-4 levels. Dose calculations, toxicity and adverse reaction profiles, and overall survival were analyzed.</p><p>Results</p><p>Obese patients were younger at the diagnosis of prostate cancer and had a shorter duration from diagnosis to docetaxel therapy. Analysis of body composition found that a high visceral fat-to-subcutaneous fat area ratio (VSR) was associated with poor prognosis but a high visceral fat-to-muscle area ratio (VMR) and high body mass index were associated with increased duration from starting docetaxel to death, allowing such men to catch up with patients with normal body mass index in overall survival from cancer diagnosis to death. Cox proportional hazard regression showed that age ≥65 years, high VSR, abnormal serum alkaline phosphatase, and >10% reduction of initial dosage were significant predictors of shorter time between starting docetaxel and death, and that high VMR, obesity, and weekly regimens were significant predictors of longer survival after docetaxel.</p><p>Conclusion</p><p>Obese and overweight patients may benefit more from weekly docetaxel regimens using the reference dosage of 35 mg/m² without empirical dosage reduction.</p></div

Time-related differences among groups of prostate cancer patients with different BMIs who received weekly docetaxel treatment or other docetaxel regimens.

<p>Box plots are shown for the following parameters: A) age at diagnosis of prostate cancer, B) age at initiation of docetaxel treatment, C) the number of years after diagnosis of prostate cancer when docetaxel treatment was initiated, and D) the number of months of follow-up starting from the initiation of docetaxel therapy. The black line inside each box represents the median, and outliers are represented by circles beyond the whiskers. The patient groups are as labeled beneath the horizontal axes. The groups that received weekly docetaxel regimens are shown in white, and those received other regimens are shown in red. The blue lines with <i>P</i> values labeled next to each indicate significant (<i>P</i> < 0.05) intergroup comparisons. The <i>P</i> values were based on non-parametric one-way ANOVA (Kruskal-Wallis) with post-hoc intergroup comparisons using the Tukey test.</p

Overall survival of metastatic prostate cancer patients starting docetaxel treatment.

<p>A) Univariate Kaplan-Meier survival functions for overall survival starting from the initiation of docetaxel treatment to the event of death are shown for patients in different BMI categories as labeled. Each + represents a censored data point. B) Univariate Kaplan-Meier survival functions for overall survival are shown for all patients in the study cohort grouped by VSR (upper left). Stratified by BMI categories (<25, 25–30, and >30 kg/m² for the lower left, upper right, and lower right subpanels, respectively), the survival functions for patients in each BMI category are shown for the different VSR groups as labeled. Each + represents a censored data point.</p