A PK/PD study of Delta-4 abiraterone metabolite in metastatic castration-resistant prostate cancer patients

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
B BlanchetJ Alexandre

Abstract

Δ4-abiraterone (Δ4A) is an activemetabolite of abiraterone (ABI), which is approved in the treatment of metastatic castration resistant prostate cancer (mCRPC). The contribution of Δ4A to the clinical antitumor activity of ABI remains unknown. The aim of this study was to explore the relationship between plasma Δ4A concentration and survival in 36 mCRPC patients treated with abiraterone acetate (1000 mg/day) plus prednisone (10 mg/day). Plasma trough ABI and Δ4A concentrations were monthly assayed using liquid chromatography during the first 3 months of treatment. ABI and Δ4A 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 Δ4A Cmin were 12.6 ± 6.8 ng/mL and 1.6 ± 1.3 ng/mL, respectively. The mean metabolic ratio Δ4A/ABI was of 0.18 ± 0.25. In regard with in vitro pharmacodynamic data, effective plasma concentrations for ABI and Δ4A were reached in 30 patients (83.3%) and only 2 patients (5.6%), respectively. Higher Δ4A 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 th...Continue Reading

Citations

Jul 12, 2020·Biomedical Chromatography : BMC·Thaís Luise Dillenburg WeissSimone Gasparin Verza
Dec 30, 2020·Journal of Pharmaceutical and Biomedical Analysis·Thaís Luise Dillenburg WeissSimone Gasparin Verza
Aug 20, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Bárbara MatosMargarida Fardilha

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