ABSTRACT &Dgr;4‐abiraterone (&Dgr;4A) is an activemetabolite of abiraterone (ABI), which is approved in the treatment of metastatic castration resistant prostate cancer (mCRPC). The contribution of &Dgr;4A to the clinical antitumor… Click to show full abstract
ABSTRACT &Dgr;4‐abiraterone (&Dgr;4A) is an activemetabolite of abiraterone (ABI), which is approved in the treatment of metastatic castration resistant prostate cancer (mCRPC). The contribution of &Dgr;4A to the clinical antitumor activity of ABI remains unknown. The aim of this study was to explore the relationship between plasma &Dgr;4A concentration and survival in 36 mCRPC patients treated with abiraterone acetate (1000 mg/day) plus prednisone (10 mg/day). Plasma trough ABI and &Dgr;4A concentrations were monthly assayed using liquid chromatography during the first 3 months of treatment. ABI and &Dgr;4A Cmin were defined as the mean of trough concentrations measured for each patient. Predictive factors regarding progression‐free survival (PFS) and overall survival (OS) were explored using univariate Cox model. Mean plasma ABI and &Dgr;4A Cmin were 12.6 ± 6.8 ng/mL and 1.6 ± 1.3 ng/mL, respectively. The mean metabolic ratio &Dgr;4A/ABI was of 0.18 ± 0.25. In regard with in vitro pharmacodynamic data, effective plasma concentrations for ABI and &Dgr;4A were reached in 30 patients (83.3%) and only 2 patients (5.6%), respectively. Higher &Dgr;4A Cmin was associated with shorter OS (Hazard ratio, HR 1.54; CI95% 1.06–2.22; p = 0.022) but not with PFS. The HR associated with the metabolic &Dgr;4A/ABI ratio for PFS and OS were 7.80 (CI 95% 1.63–37.38; p = 0.010) and 12.52 (CI 95% 1.95–80.47, p = 0.0078), respectively. The present study shows &Dgr;4A is unlikely to have meaningful contribution to pharmacodynamic activity of ABI in mCPRC, rather that higher plasma &Dgr;4A concentration is associated with worse clinical outcomes. A high &Dgr;4A/ABI metabolic ratio could help to identify mCRPC patients with poorer survival.
               
Click one of the above tabs to view related content.