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 |
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| Institution: | 1. Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, Toronto, Canada;2. Division of Biostatistics, Princess Margaret Cancer Center, University Health Network, Toronto, Canada;1. Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, United Kingdom;2. William Harvey Hospital, Ashford, Kent TN24 0LZ, United Kingdom;3. Woolfson Institute of Preventative Medicine, Charterhouse Sq., London EC1M 6BQ, United Kingdom;4. Division of Cancer Studies, King’s College London, 3rd Floor Bermondsey Wing, Guy’s Hospital, London SE1 9RT, United Kingdom;1. Tulane University School of Medicine, New Orleans, LA;2. Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA;3. Department of Internal Medicine, University of Massachusetts Medical School, Worcester, MA;4. Department of Urology, Tulane University School of Medicine, New Orleans, LA;5. Departments of Medicine and Urology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA;1. Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy;2. Hospital Universitario 12 de Octubre, Madrid, Spain;3. Rigshospitalet, Copenhagen, Denmark;4. National Institute of Oncology, Budapest, Hungary;5. McMaster University, Hamilton, ON, Canada;6. ICON Cancer Care, Brisbane, QLD, Australia;7. University of Montreal, Montreal, QC, Canada;8. Center for Oncology, Hospital Sírio-Libanês, São Paulo, Brazil;9. OncoCare Cancer Centre, Singapore;10. Centro Oncologico Belenus, Cuernavaca, Mexico;11. University of Pisa, Pisa, Italy;12. Janssen Research & Development, Horsham, PA, USA;13. Janssen Scientific Affairs, Horsham, PA, USA;14. Janssen Research & Development, Beerse, Belgium;15. Janssen Research & Development, Los Angeles, CA, USA;p. Janssen Global Services, Raritan, NJ, USA;q. Janssen Research & Development, Menlo Park, CA, USA;r. Duke Cancer Institute, Durham, NC, USA;1. Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY;2. Sanofi US, Bridgewater, NJ;3. Groupe d''Analyse, Ltée, Montréal, Quebec, Canada;4. Analysis Group, Inc, Boston, MA;1. Department of Medical Oncology, Cochin Hospital, Paris Descartes University, CARPEM, AP-HP, Paris, France;2. Pharmacokinetics and Pharmacochemistry Unit, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France;3. Department of Genetics, Institut Curie, Paris, France;4. Department of Urology, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France;5. Biochemistry Unit, Georges Pompidou European Hospital, Paris Descartes University, AP-HP, Paris, France;6. Hormonology Laboratory, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France |
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| Abstract: | IntroductionAbiraterone (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.ObjectiveTo study outcomes of men with mCRPC treated with low-dose AA and/or with prior exposure to KT.Patients and methodsRetrospective 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.ResultsIn 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).ConclusionsLow-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. |
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| Keywords: | Abiraterone Dosing Ketoconazole mCRPC Response rate |
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