title: Relation between plasma trough concentration of abiraterone and prostate-specific antigen response in metastatic castration-resistant prostate cancer patients.
abstract: Abiraterone (ABI) is a major oral agent for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients but its systemic exposure is subject to a large inter-individual variability. We aimed to explore the relationship between ABI trough plasma concentration and prostate-specific antigen (PSA) response in mCRPC patients and to identify the critical determinants for its activity.
  
  
  
  This is a monocentric prospective observational study in mCRPC patients treated with ABI. The plasmatic concentration of ABI at steady state was measured using liquid chromatography with fluorescence detection. The primary objective was to study the relationship between mean ABI plasma exposure (ABI Cmin) and 3-month PSA response.
  
  
  
  From 2012 to 2016, 61 mCRPC patients were eligible for pharmacokinetic/pharmacodynamic assessment. Thirty-eight patients experienced PSA response (62%, [confidence interval {CI} 95% 50-78]). In univariate analysis, ABI Cminwas 1.5-fold higher in responders: 12.0 ng/mL (CI 95% 9.4-15.6) versus 8.0 ng/mL (CI 95% 5.8-11.6; P = 0.0015). In multivariate analysis, only ABI Cminwas independently associated with PSA response (odds ratio = 1.12 [CI 95% 1.01-1.25], P = 0.004). By receiver operating characteristic analysis, the optimal threshold for ABI Cminwas 8.4 ng/mL. Progression-free survival (PFS) was significantly higher in patients with ABI Cminabove 8.4 ng/mL (hazard ratio 0.55, [CI 95% 0.31-0.99], 12.2 [CI 95% 9.2-19.5] versus 7.4 [CI 95% 5.5-14.7] months otherwise, P = 0.044).
  
  
  
  We showed that ABI trough concentration correlates with PSA response and PFS. Moreover, we could determine a cut-off value of plasmatic concentration for PSA response. Altogether, ABI concentration monitoring appears as a new approach to improve clinical outcome in mCPRC patients.
authors.affiliation: Department of Medical Oncology, Cochin Hospital, Paris Descartes University, CARPEM, AP-HP, Paris, France. Electronic address: carton.edith@gmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Carton
authors.affiliation: Pharmacokinetics and Pharmacochemistry Unit, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Noe
authors.affiliation: Department of Medical Oncology, Cochin Hospital, Paris Descartes University, CARPEM, AP-HP, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Huillard
authors.affiliation: Department of Genetics, Institut Curie, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Golmard
authors.affiliation: Department of Medical Oncology, Cochin Hospital, Paris Descartes University, CARPEM, AP-HP, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Giroux
authors.affiliation: Department of Medical Oncology, Cochin Hospital, Paris Descartes University, CARPEM, AP-HP, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Cessot
authors.affiliation: Department of Medical Oncology, Cochin Hospital, Paris Descartes University, CARPEM, AP-HP, Paris, France.
authors.forename: N E B
authors.initials: NE
authors.lastname: Saidu
authors.affiliation: Department of Urology, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Peyromaure
authors.affiliation: Department of Urology, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Zerbib
authors.affiliation: Biochemistry Unit, Georges Pompidou European Hospital, Paris Descartes University, AP-HP, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Narjoz
authors.affiliation: Hormonology Laboratory, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Guibourdenche
authors.affiliation: Pharmacokinetics and Pharmacochemistry Unit, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Pharmacokinetics and Pharmacochemistry Unit, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Vidal
authors.affiliation: Department of Medical Oncology, Cochin Hospital, Paris Descartes University, CARPEM, AP-HP, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Goldwasser
authors.affiliation: Pharmacokinetics and Pharmacochemistry Unit, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Blanchet
authors.affiliation: Department of Medical Oncology, Cochin Hospital, Paris Descartes University, CARPEM, AP-HP, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Alexandre
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000736:Androstenes / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy*
chemical_list: D000726:Androgen Antagonists; D000736:Androstenes; D017430:Prostate-Specific Antigen; C089740:abiraterone
keywords: Abiraterone acetate; Drug monitoring; Metastatic castration-resistant prostate carcinoma; PSA response; Trough concentration