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 Journal Article


Authors: Fizazi, K.; Chi, K. N.; de Bono, J. S.; Gomella, L. G.; Miller, K.; Rathkopf, D. E.; Ryan, C. J.; Scher, H. I.; Shore, N. D.; De Porre, P.; Londhe, A.; McGowan, T.; Pelhivanov, N.; Charnas, R.; Todd, M. B.; Montgomery, B.
Article 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: Background 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. Objective 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. Design, setting, and participants 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. Intervention All 2267 patients received 5 mg of P twice daily, and 1333/2267 received AA (1 g) plus P. Results and limitations 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. Conclusions 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. Patient summary 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. © 2016 European Association of Urology
Keywords: adult; controlled study; aged; major clinical study; prednisone; drug tolerability; drug safety; drug withdrawal; gastrointestinal hemorrhage; side effect; treatment duration; outcome assessment; low drug dose; metastasis; clinical assessment; obesity; hyperglycemia; purpura; stomach ulcer; diabetes mellitus; glucocorticoid; glucose blood level; cataract; glucose; osteoporosis; abiraterone acetate; corticosteroid; melena; fragility fracture; adverse drug reaction; skin bleeding; hematemesis; ecchymosis; rectum hemorrhage; skin atrophy; duodenum ulcer; rib fracture; castration resistant prostate cancer; hip fracture; myopathy; osteopenia; adrenal insufficiency; weight gain; corticosteroids; adverse events; impaired glucose tolerance; peptic ulcer; long term exposure; long term; tolerability; compression fracture; glucosuria; healing impairment; stomach hemorrhage; spine fracture; wrist fracture; upper gastrointestinal bleeding; metastatic castration-resistant prostate cancer; human; male; priority journal; article; cushingoid syndrome; erosive gastritis; feces discoloration; femoral neck fracture; skin fragility; stria; subcutaneous hemorrhage
Journal Title: European Urology
Volume: 70
Issue: 3
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2016-09-01
Start Page: 438
End Page: 444
Language: English
DOI: 10.1016/j.eururo.2016.02.035
PROVIDER: scopus
PUBMED: 26965562
DOI/URL:
Notes: Article -- Export Date: 1 November 2016 -- Source: Scopus
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MSK Authors
  1. Dana Elizabeth Rathkopf
    144 Rathkopf
  2. Howard Scher
    834 Scher