TY - JOUR
T1 - New therapies for castration-resistant prostate cancer
T2 - Efficacy and safety
AU - Beltran, Himisha
AU - Beer, Tomasz M.
AU - Carducci, Michael A.
AU - De Bono, Johann
AU - Gleave, Martin
AU - Hussain, Maha
AU - Kelly, William K.
AU - Saad, Fred
AU - Sternberg, Cora
AU - Tagawa, Scott T.
AU - Tannock, Ian F.
N1 - Funding Information:
K/year. M.G. has submitted patent for OGX-011 (licensed to OncoGenex Technologies), and receives research grant support from OncoGenex, Pfizer, Astra Zeneca, Takeda. W.K.K. is consultant for Dendreon and Novartis, and has received research support from Roche-Genentech. F.S. has served as advisor for Amgen, Novartis, Sanofi Aventis, Astellas, Janssen, AstraZeneca, Millenium. C.S has received Research funding from Cougar Biotech and Medivation, Honoraria from Johnson & Johnson, Astellas, Amgen, Sanofi-Aventis. S.T.T is on speaker's bureau for Amgen and has received Honoraria from Sanofi-Aventis. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: T.M.B. has served as consultant for Ascenta Therapeutics, Centocor Ortho Biotech Services LLC, Dendreon, GTx Inc, received research funding from Bayer, Bristol-Myers Squibb, Cell Therapeutics Inc., Cougar Biotechnology, Dendreon, ImClone, Medarex, Medivation Inc., Novartis, OncoGenex, Sanofi-Aventis, Kuni, and is on Speakers Bureau for Sanofi-Aventis, Honoraria received from Sanofi-Aventis, patent with Receptor Therapeutics, and Expert testimony for Novartis. M.C. has served as consultant with Sanofi- Aventis, Pfizer, Bayer, Novartis, Medivation <10
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
KW - AR
KW - Abiraterone acetate
KW - Cabazitaxel
KW - Castration resistance
KW - Chemotherapy
KW - Denosumab
KW - Immunotherapy
KW - Novel hormonal therapy
KW - Prostate cancer
KW - Sipuleucel-T
KW - Targeted therapy
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UR - http://www.scopus.com/inward/citedby.url?scp=79959535385&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2011.04.038
DO - 10.1016/j.eururo.2011.04.038
M3 - Review article
C2 - 21592649
AN - SCOPUS:79959535385
SN - 0302-2838
VL - 60
SP - 279
EP - 290
JO - European Urology
JF - European Urology
IS - 2
ER -