title: Abiraterone acetate in metastatic castration-resistant prostate cancer: a retrospective review of the Princess Margaret experience of (I) low dose abiraterone and (II) prior ketoconazole.
abstract: BACKGROUND
  Abiraterone (AA) is a CYP17 inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC). Data suggest similar pharmacokinetics of 250-500 mg of AA with high-fat meals ('low-dose') and 1000 mg in the fasting state ('full-dose'). Ketoconazole (KT) is a less potent CYP17 inhibitor previously widely used in mCRPC.
  
  
  OBJECTIVE
  To study outcomes of men with mCRPC treated with low-dose AA and/or with prior exposure to KT.
  
  
  METHODS
  Retrospective chart review of all men treated with AA at the Princess Margaret Cancer Centre between November 2009 and March 2013. Outcome measures were prostate-specific antigen response rate (PSA-RR), biochemical progression-free survival (bPFS), treatment duration and overall survival (OS). Associations between AA dose or prior KT and outcomes were assessed using chi-square test for PSA-RR and log-rank test for bPFS, treatment duration and OS.
  
  
  RESULTS
  In total, 111 men who received AA were evaluable, of which 21 received low-dose AA and 23 received prior KT. There was a non-significant difference in PSA-RR (43% versus 32%, p=0.37), but no significant differences in median bPFS, median treatment duration and median OS (18.7 versus 16.6 months, p=0.25) in the full and low-dose cohorts respectively, and for those who received prior KT or not (PSA-RR 48% versus 38%, p=0.4; median OS 24.2 versus 16.5 months, p=0.066, respectively).
  
  
  CONCLUSIONS
  Low-dose AA or prior KT treatment were not associated with poorer outcome in men with mCRPC treated with AA. These observations may have implications for drug sequencing and dose in resource-limited settings.
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, Toronto, Canada.
authors.forename: Raya
authors.initials: R
authors.lastname: Leibowitz-Amit
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, Toronto, Canada.
authors.forename: Jo-An
authors.initials: JA
authors.lastname: Seah
authors.affiliation: Division of Biostatistics, Princess Margaret Cancer Center, University Health Network, Toronto, Canada.
authors.forename: Eshetu G
authors.initials: EG
authors.lastname: Atenafu
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, Toronto, Canada.
authors.forename: Arnoud J
authors.initials: AJ
authors.lastname: Templeton
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, Toronto, Canada.
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Vera-Badillo
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, Toronto, Canada.
authors.forename: Nimira
authors.initials: N
authors.lastname: Alimohamed
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, Toronto, Canada.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, Toronto, Canada.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Tannock
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, Toronto, Canada.
authors.forename: Srikala S
authors.initials: SS
authors.lastname: Sridhar
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, Toronto, Canada. Electronic address: Anthony.joshua@uhn.ca.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Joshua
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes; D000737:Androstenols / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000736:Androstenes; D000737:Androstenols; C089740:abiraterone; D007654:Ketoconazole
keywords: Abiraterone; Dosing; Ketoconazole; Response rate; mCRPC