title: Low Incidence of Corticosteroid-associated Adverse Events on Long-term Exposure to Low-dose Prednisone Given with Abiraterone Acetate to Patients with Metastatic Castration-resistant Prostate Cancer.
abstract: Abiraterone acetate (AA) is the prodrug of abiraterone, which inhibits CYP17A1 and testosterone synthesis and prolongs the survival of patients with metastatic castration-resistant prostate cancer (mCRPC). AA plus prednisone (P) (AA+P) is approved for the treatment of patients with mCRPC.
  
  
  
  To investigate whether long-term use of low-dose P with or without AA leads to corticosteroid-associated adverse events (CA-AEs) in mCRPC patients.
  
  
  
  The study included 2267 patients in COU-AA-301 and COU-AA-302. We used an inclusive Standardized MedDRA Queries-oriented approach to identify 112 preferred terms for known CA-AEs, and assessed the incidence of CA-AEs during 3-mo exposure intervals and across all P exposure levels.
  
  
  
  All 2267 patients received 5mg of P twice daily, and 1333/2267 received AA (1g) plus P.
  
  
  
  The CA-AE incidence after any P exposure was 25%, 26%, and 23% for any grade, and 5%, 5%, and 4% for grade ≥3 CA-AEs for all patients and the AA+P and P alone groups, respectively. The most common any-grade CA-AEs were hyperglycemia (7.4%, 7.8%, and 6.9% for all patients, AA+P, and P alone, respectively) and weight increase (4.3%, 3.9%, and 4.8%, respectively). When assessed by duration of exposure (3-mo intervals up to ≥30 mo), no discernable trend was observed for CA-AEs, including hyperglycemia and weight increase. The investigator-reported study discontinuation rate due to CA-AEs was 11/2267 (0.5%), and one patient had a CA-AE resulting in death.
  
  
  
  Low-dose P given with or without AA is associated with low overall incidence of CA-AEs. The frequency of CA-AEs remained low with increased duration of exposure to P.
  
  
  
  We assessed adverse events in patients with metastatic castration-resistant prostate cancer during long-term treatment with a low dose of a corticosteroid. We found that long-term treatment with this low-dose corticosteroid is safe and tolerable.
authors.affiliation: Institut Gustave Roussy, University of Paris Sud, Villejuif, France. Electronic address: karim.fizazi@igr.fr.
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: BC Cancer Agency, Vancouver, BC, Canada.
authors.forename: Kim N
authors.initials: KN
authors.lastname: Chi
authors.affiliation: The Institute of Cancer Research and The Royal Marsden Hospital, Sutton, UK.
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.affiliation: Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Leonard G
authors.initials: LG
authors.lastname: Gomella
authors.affiliation: Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.affiliation: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
authors.forename: Dana E
authors.initials: DE
authors.lastname: Rathkopf
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ryan
authors.affiliation: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.affiliation: Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Shore
authors.affiliation: Janssen Research & Development, Beerse, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: De Porre
authors.affiliation: Janssen Research & Development, Horsham, PA, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Londhe
authors.affiliation: Janssen Scientific Affairs, Horsham, PA, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: McGowan
authors.affiliation: Janssen Research & Development, Raritan, NJ, USA.
authors.forename: Nonko
authors.initials: N
authors.lastname: Pelhivanov
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Charnas
authors.affiliation: Janssen Global Services, Raritan, NJ, USA.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Todd
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Montgomery
mesh_terms: D000069501:Abiraterone Acetate / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000069501:Abiraterone Acetate; D011241:Prednisone
keywords: Abiraterone acetate; Adverse events; Corticosteroids; Glucocorticoid; Long term; Metastatic castration-resistant prostate cancer; Tolerability