Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer Journal Article


Authors: Danila, D. C.; Morris, M. J.; de Bono, J. S.; Ryan, C. J.; Denmeade, S. R.; Smith, M. R.; Taplin, M. E.; Bubley, G. J.; Kheoh, T.; Haqq, C.; Molina, A.; Anand, A.; Koscuiszka, M.; Larson, S. M.; Schwartz, L. H.; Fleisher, M.; Scher, H. I.
Article Title: Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer
Abstract: Purpose Persistence of ligand-mediated androgen receptor signaling has been documented in castration-resistant prostate cancers (CRPCs). Abiraterone acetate (AA) is a potent and selective inhibitor of CYP17, which is required for androgen biosynthesis in the testes, adrenal glands, and prostate tissue. This trial evaluated the efficacy and safety of AA in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with AA monotherapy. Patients and Methods Fifty-eight men with progressive metastatic CRPC who experienced treatment failure with docetaxel-based chemotherapy received AA (1,000 mg daily) with prednisone (5 mg twice daily). Twenty-seven (47%) patients had received prior ketoconazole. The primary outcome was >= 50% prostate-specific antigen (PSA) decline, with objective response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and changes in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and circulating tumor cell (CTC) numbers. Safety was also evaluated. Results A >= 50% decline in PSA was confirmed in 22 (36%) patients, including 14 (45%) of 31 ketoconazole-naive and seven (26%) of 27 ketoconazole-pretreated patients. Partial responses were seen in four (18%) of 22 patients with RECIST-evaluable target lesions. Improved ECOG PS was seen in 28% of patients. Median time to PSA progression was 169 days (95% CI, 82 to 200 days). CTC conversions with treatment from >= 5 to < 5 were noted in 10 (34%) of 29 patients. The majority of AA-related adverse events were grade 1 to 2, and no AA-related grade 4 events were seen. Conclusion AA plus prednisone was well tolerated, with encouraging antitumor activity in heavily pretreated CRPC patients. The incidence of mineralocorticoid-related toxicities (hypertension or hypokalemia) was reduced by adding low-dose prednisone. The combination of AA plus prednisone is recommended for phase III investigations.
Keywords: survival; progression; end-points; testosterone; trial; expression; circulating tumor-cells; adrenal androgens; dose ketoconazole; cyp17
Journal Title: Journal of Clinical Oncology
Volume: 28
Issue: 9
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2010-03-20
Start Page: 1496
End Page: 1501
Language: English
ACCESSION: ISI:000275824600010
DOI: 10.1200/jco.2009.25.9259
PROVIDER: wos
PMCID: PMC3040042
PUBMED: 20159814
Notes: --- - Article - "Source: Wos"
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MSK Authors
  1. Michael Morris
    274 Morris
  2. Lawrence H Schwartz
    281 Schwartz
  3. Steven M Larson
    766 Larson
  4. Martin Fleisher
    237 Fleisher
  5. Howard Scher
    818 Scher
  6. Daniel C Danila
    82 Danila
  7. Aseem Anand
    45 Anand