CONTEXT: Prostate cancer (PCa) is the most common noncutaneous malignancy and the second leading cause of cancer mortality amongst men in the Western world. Up to 40% of men diagnosed with PCa will eventually develop metastatic disease, and although most respond to initial medical or surgical castration, progression to castration resistance is universal. The average survival for patients with castration-resistant prostate cancer (CRPC) is 2-3 yr. OBJECTIVE: To discuss the biologic rationale and evidence supporting current management of patients with CRPC and to review promising novel agents. EVIDENCE ACQUISITION: Electronic databases (PubMed, ClinicalTrials.gov), relevant journals, and conference proceedings were searched manually for preclinical studies, clinical trials, and biomarker analyses focused on the treatment of CRPC. Keywords included castrate resistant prostate cancer and: targeted therapy, novel therapy, immunotherapy, androgen therapy, bone therapy, mechanisms, biomarkers, and trial endpoints; no time range was specified. Information pertaining to current studies was discussed with key opinion leaders. EVIDENCE SYNTHESIS: We focus on the efficacy and safety of approved agents, promising therapies that have proceeded to phase 3 evaluation, and those that have enhanced our understanding of the biology of CRPC. Biomarkers are considered in the context of novel targeted agents and immunotherapy. CONCLUSIONS: CRPC has many targets. Four new agents with different mechanisms of action have recently been shown to have positive results in large phase 3 randomized trials, and have already been approved in the United States for CRPC: cabazitaxel, sipuleucel-T, denosumab, and abiraterone acetate. With our improved understanding of tumor biology and the incorporation of new prognostic and molecular biomarkers into clinical trials, we are making progress in the management of patients with CRPC.
CONTEXT: Prostate cancer (PCa) is the most common noncutaneous malignancy and the second leading cause of cancer mortality amongst men in the Western world. Up to 40% of men diagnosed with PCa will eventually develop metastatic disease, and although most respond to initial medical or surgical castration, progression to castration resistance is universal. The average survival for patients with castration-resistant prostate cancer (CRPC) is 2-3 yr. OBJECTIVE: To discuss the biologic rationale and evidence supporting current management of patients with CRPC and to review promising novel agents. EVIDENCE ACQUISITION: Electronic databases (PubMed, ClinicalTrials.gov), relevant journals, and conference proceedings were searched manually for preclinical studies, clinical trials, and biomarker analyses focused on the treatment of CRPC. Keywords included castrate resistant prostate cancer and: targeted therapy, novel therapy, immunotherapy, androgen therapy, bone therapy, mechanisms, biomarkers, and trial endpoints; no time range was specified. Information pertaining to current studies was discussed with key opinion leaders. EVIDENCE SYNTHESIS: We focus on the efficacy and safety of approved agents, promising therapies that have proceeded to phase 3 evaluation, and those that have enhanced our understanding of the biology of CRPC. Biomarkers are considered in the context of novel targeted agents and immunotherapy. CONCLUSIONS: CRPC has many targets. Four new agents with different mechanisms of action have recently been shown to have positive results in large phase 3 randomized trials, and have already been approved in the United States for CRPC: cabazitaxel, sipuleucel-T, denosumab, and abiraterone acetate. With our improved understanding of tumor biology and the incorporation of new prognostic and molecular biomarkers into clinical trials, we are making progress in the management of patients with CRPC.
Authors: Y Zhao; J J Lv; J Chen; X B Jin; M W Wang; Z H Su; L Y Wang; H Y Zhang Journal: Prostate Cancer Prostatic Dis Date: 2016-07-19 Impact factor: 5.554
Authors: Romana Mikyskova; Marie Indrova; Ivan Stepanek; Ivan Kanchev; Jana Bieblova; Sarka Vosahlikova; Irena Moserova; Iva Truxova; Jitka Fucikova; Jirina Bartunkova; Radek Spisek; Radislav Sedlacek; Milan Reinis Journal: Oncoimmunology Date: 2017-08-24 Impact factor: 8.110
Authors: Philipp Nuhn; Ajay M Vaghasia; Jatinder Goyal; Xian C Zhou; Michael A Carducci; Mario A Eisenberger; Emmanuel S Antonarakis Journal: BJU Int Date: 2014-02-14 Impact factor: 5.588
Authors: James P Dean; Cynthia C Sprenger; Junxiang Wan; Kathleen Haugk; William J Ellis; Daniel W Lin; John M Corman; Bruce L Dalkin; Elahe Mostaghel; Peter S Nelson; Pinchas Cohen; Bruce Montgomery; Stephen R Plymate Journal: J Clin Endocrinol Metab Date: 2013-03-26 Impact factor: 5.958