Relationship between changes in serum androgen level measured by LC-MS/MS and therapeutic effect after enzalutamide treatment.

Abstract

88 Background: Enzalutamide (ENZ) has proven efficacy against castration-resistant prostate cancer (CRPC) and is widely used in treatment. However, no useful biomarkers have yet been reported to predict the effects of ENZ. We examined the relationship between the efficacy of ENZ and changes in serum androgen levels after ENZ administration. Methods: This exploratory research was based on the data from our prospective clinical trial. Of a total of 104 cases, 67 with confirmed changes in androgen levels after 3 months of ENZ administration, compared to pretreatment levels, were included in this study to identify prognostic factors. Serum androgen levels were measured by liquid chromatography-mass spectrometry (LC-MS/MS). This study was approved by the institutional review board of Gunma University Hospital (No.1177). Results: The study population of 67 patients had a median age of 73 years. The median serum levels of testosterone (T), dihydrotestosterone (DHT), androstenedione (A-dione), and dehydroepiandrosterone sulfate (DHEA-S) before treatment were 56.8 pg/ml, 7.8 pg/ml, 253.5 pg/ml, and 502.2 pg/ml, respectively. The median increase rate(%) of T, DHT, A-dione andDHEA-S after 3 months of ENZ administration were +55.5%, +49.5%, +25.8%, and +24.9%, respectively. T, DHT, and A-dione levels were significantly increased after 3 months (p < 0.05). We performed Cox regression analysis to predict PSA-PFS and OS. Hemoglobin (Hb, ≥ 12.5 g/dl vs. < 12.5 g/dl) and T increase rate ( < 55.5% vs. ≥ 55.5%) were significant predictors of PSA-PFS (p < 0.05). ECOG performance status (0 vs. 1 - 2, respectively) and Hb (≥ 12.5 vs. < 12.5 g/dl, respectively) and T ( < 55.5% vs. ≥55.5%) were significant predictors of OS (p < 0.05). Conclusions: PSA-PFS and OS were significantly poor in the cases in which T increased significantly 3 months after ENZ administration. It was suggested that the change of hormonal environment after ENZ administration may be a prognostic factor.