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van Nuland, M; Groenland, S L; Bergman, A M; Steeghs, N; Rosing, H; Venekamp, N; Huitema, A D R; Beijnen, J H
Prostate cancer and prostatic diseases, 06/2020, Letnik: 23, Številka: 2Journal Article
Abiraterone acetate is an oral 17α-hydroxylase/C17,20-lyase (CYP17) inhibitor approved for the treatment of metastatic castration-resistant prostate cancer (mCPRC) patients. Previously, a prospective observational trial demonstrated a relationship between abiraterone trough concentrations (C ) in plasma and treatment efficacy. The aim of our study was to investigate the exposure-response relationship of abiraterone and its metabolites, and to study if the proposed target for abiraterone of 8.4 ng/mL is feasible in a "real-world" patient cohort. mCRPC patients who had at least one abiraterone plasma concentration at steady-state were included in this study. Plasma abiraterone and its metabolites levels were analyzed using a validated liquid chromatography-mass spectrometry method. Using calculated C values of abiraterone and its active metabolite Δ(4)-abiraterone (D4A), univariate, and multivariable Cox regression analyses were performed. Sixty-two patients were included in this retrospective analysis, of which 42% were underexposed (mean abiraterone C ≤ 8.4 ng/mL). In multivariable analysis, C ≥ 8.4 ng/mL was associated with longer prostate-specific antigen (PSA) independent progression-free survival (16.9 vs 6.1 months; p = 0.033), which resulted in a hazard ratio of 0.44 (95% confidence interval: 0.23-0.82, p = 0.01). D4A C did not show a relationship with treatment efficacy. Our study shows that mCRPC patients with an abiraterone C ≥ 8.4 ng/mL have a better prognosis compared with patients with low C . Monitoring C of abiraterone can help to identify those patients at risk of suboptimal treatment for whom treatment optimization may be appropriate.
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in: SICRIS
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