Abstract
BackgroundDocetaxel, 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.MethodsWe 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.ResultsObese 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.ConclusionObese and overweight patients may benefit more from weekly docetaxel regimens using the reference dosage of 35 mg/m2 without empirical dosage reduction.
Highlights
Prostate cancer is the most commonly diagnosed cancer in men in the United States and the second most common worldwide
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
We found that the overweight and obese patients were diagnosed at a younger age and developed metastatic disease that was treated with docetaxel earlier than normal body mass index (BMI) patients, but they died at about the same time after diagnosis as the normal BMI patients
Summary
Prostate cancer is the most commonly diagnosed cancer in men in the United States and the second most common worldwide. In men with metastatic or recurrent prostate cancer, androgen-deprivation therapy (ADT) is first-line therapy to reduce morbidity and improve survival [1]. The hypogonadal state changes body mass composition. ADT given for 12 months significantly decreases muscle and bone mass and increases fat mass, resulting in a net weight gain [2, 3]. A longitudinal study has shown that prostate cancer patients on ADT gain about 2.2 kg in weight during the first year of therapy and remain stable at that higher weight thereafter [4]. 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
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