New therapies for castration-resistant prostate cancer: Efficacy and safety

Himisha Beltran, Tomasz (Tom) Beer, Michael A. Carducci, Johann De Bono, Martin Gleave, Maha Hussain, William K. Kelly, Fred Saad, Cora Sternberg, Scott T. Tagawa, Ian F. Tannock

    Research output: Contribution to journalArticle

    103 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)279-290
    Number of pages12
    JournalEuropean Urology
    Volume60
    Issue number2
    DOIs
    StatePublished - Aug 2011

    Fingerprint

    Castration
    Prostatic Neoplasms
    Safety
    Biomarkers
    Therapeutics
    Immunotherapy
    Clinical Trials
    Western World
    Second Primary Neoplasms
    PubMed
    Androgens
    Neoplasms
    Databases
    Bone and Bones
    Survival
    Mortality

    Keywords

    • Abiraterone acetate
    • AR
    • Cabazitaxel
    • Castration resistance
    • Chemotherapy
    • Denosumab
    • Immunotherapy
    • Novel hormonal therapy
    • Prostate cancer
    • Sipuleucel-T
    • Targeted therapy

    ASJC Scopus subject areas

    • Urology

    Cite this

    Beltran, H., Beer, T. T., Carducci, M. A., De Bono, J., Gleave, M., Hussain, M., ... Tannock, I. F. (2011). New therapies for castration-resistant prostate cancer: Efficacy and safety. European Urology, 60(2), 279-290. https://doi.org/10.1016/j.eururo.2011.04.038

    New therapies for castration-resistant prostate cancer : Efficacy and safety. / Beltran, Himisha; Beer, Tomasz (Tom); Carducci, Michael A.; De Bono, Johann; Gleave, Martin; Hussain, Maha; Kelly, William K.; Saad, Fred; Sternberg, Cora; Tagawa, Scott T.; Tannock, Ian F.

    In: European Urology, Vol. 60, No. 2, 08.2011, p. 279-290.

    Research output: Contribution to journalArticle

    Beltran, H, Beer, TT, Carducci, MA, De Bono, J, Gleave, M, Hussain, M, Kelly, WK, Saad, F, Sternberg, C, Tagawa, ST & Tannock, IF 2011, 'New therapies for castration-resistant prostate cancer: Efficacy and safety', European Urology, vol. 60, no. 2, pp. 279-290. https://doi.org/10.1016/j.eururo.2011.04.038
    Beltran, Himisha ; Beer, Tomasz (Tom) ; Carducci, Michael A. ; De Bono, Johann ; Gleave, Martin ; Hussain, Maha ; Kelly, William K. ; Saad, Fred ; Sternberg, Cora ; Tagawa, Scott T. ; Tannock, Ian F. / New therapies for castration-resistant prostate cancer : Efficacy and safety. In: European Urology. 2011 ; Vol. 60, No. 2. pp. 279-290.
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    abstract = "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.",
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    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.

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    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.

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    KW - Sipuleucel-T

    KW - Targeted therapy

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