Changes in skeletal muscle cross sectional area (CSA) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide (ENZ).

Background: Phase III studies that led to ENZ approval in the treatment of mCRPC included side effects like fatigue, musculoskeletal pain, and falls, which could result from skeletal muscle loss. Such muscle loss (sarcopenia), in a variety of cancer populations, is correlated with mortality. While conventional androgen deprivation therapy in prostate cancer is known to cause sarcopenia, there is a paucity of data with next generation androgen receptor directed therapies like ENZ. Methods: Through query of pharmacy records, we conducted a retrospective analysis of patientstreated with ENZ prior to the use of docetaxel for mCRPC from April 28, 2011 - June 15, 2015 at Duke University. We included patients with a computed tomography (CT) scan available for analysis of skeletal muscle cross sectional area (CSA) both at baseline (+/- 6 wks) and after 6 months (+/- 6 wks) of treatment with ENZ. Muscle CSA was measured using the Slice-O-Matic (TomoVision, Montreal CA) at the level of the third lumbar vertebrae (L3) by a trained reviewer, and each measurement was verified and edited at the discretion of a second trained reviewer. The primary objective was to determine the change in muscle CSA at L3 from baseline to 6 mos of ENZ treatment (tx). Results: At the time of ENZ initiation (baseline),characteristics of 39 patients identified included a median age 74, ECOG performance status 0, BMI 30.4 kg/m2, time on ADT of 43.5 mos prior, Gleason score 8, and PSA 13.7 ng/mL. Across all time points, concordance between reviewers was high, r > 0.99. Mean CSA differed significantly from baseline (153.9 cm2, standard deviation = 30.17) to 6 months ENZ tx (145.4 cm2, standard deviation = 29.9; paired t-test p < 0.0001). In a sub-group (n = 13) with 3 measurements available (CT scan 6 mos pre-ENZ tx, baseline, and 6 mos post-ENZ tx), there was a significant change in CSA from baseline to 6 mos post-ENZ tx (paired t-test p = 0.0356), but no change from pre-ENZ tx to baseline (p = 0.1065). Conclusions: Patients treated with ENZ had significant muscle loss after six months of treatment. Prospective studies of exercise interventions to mitigate ENZ skeletal muscle toxicity are underway (NCT02256111).

Duke Scholars

Author Rajan Tilak Gupta Radiology, Abdominal Imaging

Author Yuan Wu Biostatistics & Bioinformatics, Division of Biostatistics

Author Daniel James George Medicine, Medical Oncology

Author Andrew John Armstrong Medicine, Medical Oncology

Author Michael Roger Harrison Medicine, Medical Oncology