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Updated: Aug 8, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Updates in the Treatment of Non-Metastatic Castrate-Resistant Prostate Cancer: The Benefit of Second-Generation
Matthew J Hadfield1, Vikram Lyall2, Lisa M Holle3
1Department of Medical Oncology, The Warren Alpert Medical School, Brown University, Providence, RI, USA.
Objective:
To review pharmacology, efficacy, safety, and considerations for use, of second-generation androgen receptor (AR) antagonists in treatment of nonmetastatic castrate-resistant prostate cancer (M0CRPC).
Data Sources:
Conducted search in PubMed and Google scholar (January, 1, 2002-December 31, 2022), using relevant terms.
Study Selection And Data Extraction:
Relevant English-language studies, conducted in humans evaluating second-generation AR antagonists for M0CRPC, and additional articles and package inserts were considered.
Data Synthesis:
Apalutamide, darolutamide, and enzalutamide are effective in delaying the time to development of metastatic prostate cancer in men with M0CRPC with a rapid prostate-specific antigen (PSA) doubling time (<10 months). No head-to-head, randomized, clinical trials have been conducted. The most common adverse effects include fatigue and hypertension, and quality of life is maintained in most patients. Cost is similar among the agents (~$15,000/month). Drug-drug interactions vary among these agents and should be considered, when selecting therapy as well as likely adherence. Darolutamide is administered twice daily with the others once daily.
Relevance To Patient Care And Clinical Practice:
Second-generation AR antagonists are effective in reducing time to development of metastatic disease and prolonging overall survival in patients with M0CRPC and a PSA doubling time of <10 months. Recent imaging advances may alter how we evaluate outcomes.
Conclusions:
Second-generation AR antagonists improve disease control and overall survival. Generally, they are well tolerated and QOL is maintained. Selection of the best agent is based on the adverse effect profile, potential for drug- and disease-interactions, administration, cost, and patient preference.
Insights
Second-generation androgen receptor antagonists effectively delay metastasis and prolong survival in men with nonmetastatic castrate-resistant prostate cancer (M0CRPC). These treatments are generally well-tolerated, maintaining quality of life.
Area of Science:
- Oncology
- Pharmacology
- Urology
Background:
- Nonmetastatic castrate-resistant prostate cancer (M0CRPC) is a critical stage in prostate cancer progression.
- Effective treatment strategies are needed to delay metastasis and improve survival in M0CRPC patients.
Purpose of the Study:
- To review the pharmacology, efficacy, safety, and clinical considerations of second-generation androgen receptor (AR) antagonists for M0CRPC.
- To synthesize current evidence on apalutamide, darolutamide, and enzalutamide in M0CRPC management.
Main Methods:
- Comprehensive literature search of PubMed and Google Scholar (2002-2022).
- Inclusion of English-language human studies evaluating second-generation AR antagonists for M0CRPC.
- Consideration of additional articles and drug package inserts.
Main Results:
- Second-generation AR antagonists (apalutamide, darolutamide, enzalutamide) delay metastasis in M0CRPC with rapid PSA doubling time (<10 months).
- Common side effects include fatigue and hypertension; quality of life is generally maintained.
- No head-to-head trials exist; drug interactions, administration, and cost (~$15,000/month) vary.
Conclusions:
- Second-generation AR antagonists improve disease control and prolong survival in M0CRPC patients with PSA doubling time <10 months.
- These agents are generally well-tolerated, preserving quality of life.
- Treatment selection depends on adverse effects, drug interactions, administration, cost, and patient preference.
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