Systemic Therapy in Men with Metastatic Castration-resistant Prostate Cancer: A Systematic Review |
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| Authors: | DA Loblaw C Walker-Dilks E Winquist SJ Hotte |
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| Institution: | 2. McMaster University, Hamilton, Ontario, Canada;3. London Health Sciences Centre, London, Ontario, Canada;4. Juravinski Cancer Centre, Hamilton, Ontario, Canada;1. Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands;2. Department of Urology, Radboud University Nijmegen, Medical Center, Nijmegen, the Netherlands;3. Department of Medical Oncology, Radboud University Nijmegen, Medical Center, Nijmegen, the Netherlands;4. Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands;5. Department of Internal Medicine, Isala Clinics, Zwolle, the Netherlands;6. Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands;1. Medical Oncology, S. Chiara Hospital, Largo Medaglie d’oro 1, 38122 Trento, Italy;2. Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy;1. Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;2. Memorial Sloan-Kettering Cancer Center, New York, NY, USA;3. Hellen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA;4. Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands;5. Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA;6. Janssen Research & Development, Los Angeles, CA, USA;7. Institut Gustave Roussy, University of Paris Sud, Villejuif, France;8. Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA;9. Department of Symptom Research, MD Anderson Cancer Center, Houston, TX, USA;10. Department of Genitourinary Medical Oncology, Massachusetts General Hospital, Boston, MA, USA;11. Medical Oncology, Hematology and Oncology Clinics of Australia, Brisbane, QLD, Australia;12. Janssen Global Services, Raritan, NJ, USA;13. Janssen Research & Development, Spring House, PA, USA;14. Janssen Research & Development, Raritan, NJ, USA;1. University of Montreal Hospital Center, Montreal, Quebec, Canada;2. Department of Urology, Charité Berlin, Berlin, Germany;1. Joanna Briggs Institute, University of Adelaide, Adelaide, SA, Australia;2. South Australian Prostate Cancer Clinical Outcomes Collaborative, Adelaide, SA, Australia;3. Freemasons Foundation Centre for Men''s Health, University of Adelaide, Adelaide, SA, Australia;4. Urology Unit, Repatriation General Hospital, SA Health, Adelaide, SA, Australia;5. Flinders Centre for Innovation in Cancer, Adelaide, SA, Australia;6. Centre for Population Health Research, University of South Australia, Adelaide, SA, Australia;7. Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Vic, Australia;8. Department of Radiation Oncology, Alfred Health, Adelaide, SA, Australia;9. Adelaide Radiotherapy Centre, Adelaide, SA, Australia;10. Discipline of Surgery, University of Adelaide, Adelaide, SA, Australia;1. Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China;2. College of Food and Drug, Luoyang Normal University, Luoyang, Henan 471934, PR China;3. School of Ophthalmology & Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325035, PR China;4. Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Science, Wenzhou 325001, PR China;5. School of Basic Medical Sciences, Pharmaceutical Research Center, Guangzhou Medical University, Guangzhou 511436, PR China |
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| Abstract: | AimsSince 2004, docetaxel-based chemotherapy has been the standard of care for men with metastatic castration-resistant prostate cancer (mCRPC), but recently randomised controlled trials (RCTs) of novel agents have shown promise in extending overall survival. These trials have evaluated agents delivered before chemotherapy, to replace or supplement docetaxel, or addressed treatment options for men who have progressed on docetaxel therapy. This review was undertaken to determine which systemic therapies improve cancer- or patient-related outcomes in men with mCRPC.Materials and methodsSearches were carried out in MEDLINE, EMBASE, the Cochrane Library and relevant conference proceedings. Eligible articles included RCTs comparing systemic therapy or combination (excluding primary or secondary androgen deprivation therapy, bone protective agents or radionuclides) with placebo or other agents in men with mCRPC.ResultsTwenty-five RCTs met the selection criteria. In chemotherapy-naive patients, targeted therapy with tasquinimod conferred a benefit in progression-free survival. Immunotherapy with sipuleucel-T extended overall survival and was well tolerated, but had no effect on the time to disease progression. Hypercastration with abiraterone extended progression-free survival, whereas overall survival was improved but not statistically proven. In the chemotherapy setting, updated and new trials of docetaxel alone confirmed the survival benefit seen in previous studies. A survival benefit with the addition of estramustine to docetaxel shown in a previous study did not lead to an improvement in pain palliation or quality of life. Trials of combining targeted therapies with docetaxel generally did not extend survival. The addition of bevacizumab improved progression-free survival, but not overall survival. The addition of GVAX immunotherapy or calcitriol was harmful. In the post-chemotherapy setting, progression-free and overall survival benefits were detected with cabazitaxel, abiraterone and enzalutamide. Cabazitaxel was associated with greater toxicity, whereas abiraterone and enzalutamide had less severe adverse effects. Satraplatin and sunitinib both extended progression-free survival, but did not improve overall survival.ConclusionDocetaxel-based chemotherapy remains the standard of care in men with mCRPC who are candidates for palliative systemic therapy. Promising results are emerging with sipuleucel-T and abiraterone in the pre-docetaxel setting and cabazitaxel, abiraterone and enzalutamide in patients who progress on or after docetaxel. Further research to determine the optimal choice, sequence or even the combination of these agents is necessary. |
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| Keywords: | Castration-resistant prostate cancer chemotherapy systematic review |
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