Castration-resistant prostate cancer: Treatments targeting the androgen pathway
- Nancy A Dawson, MD
Nancy A Dawson, MD
- William M Scholl Professor of Medicine and Oncology
- Lombardi Comprehensive Cancer Center
- Georgetown University
- Charles J Ryan, MD
Charles J Ryan, MD
- Professor of Clinical Medicine and Urology
- UCSF/Helen Diller Family Comprehensive Cancer
- Section Editors
- Nicholas Vogelzang, MD
Nicholas Vogelzang, MD
- Section Editor — Prostate Cancer
- Professor of Medicine
- University of Nevada School of Medicine
- US Oncology Research
- Jerome P Richie, MD, FACS
Jerome P Richie, MD, FACS
- Section Editor — Cancer of the Urethra, Penis, and Ureter; Urologic Surgery; Prostate Cancer
- Elliott Carr Cutler Professor of Surgery
- Harvard Medical School
- W Robert Lee, MD, MS, MEd
W Robert Lee, MD, MS, MEd
- Section Editor — Prostate Cancer
- Professor of Radiation Oncology
- Duke University Medical Center
Androgen deprivation therapy (ADT), either alone or in combination with chemotherapy, is generally the initial treatment for men with metastatic prostate cancer. Standard approaches to ADT include bilateral orchiectomy or medical orchiectomy using a gonadotropin releasing hormone (GnRH) agonist, which may be given alone or in combination with an antiandrogen (combined androgen blockade). (See "Initial systemic therapy for castration sensitive prostate cancer".)
Despite initial response rates of 80 to 90 percent, nearly all men eventually develop progressive disease following ADT; this is referred to as castration-resistant prostate cancer. Contemporary research in men with castration-resistant prostate cancer has led to the development of multiple agents that improved overall survival in phase III trials (table 1).
Insights into the mechanisms by which androgens stimulate growth of prostate cancer cells is leading to the development of new treatments with clinically significant activity in men with castration-resistant prostate cancer. These approaches are discussed here.
Overviews of the management of advanced castration-sensitive and castration-resistant prostate cancer are presented separately. (See "Overview of the treatment of disseminated prostate cancer".)
Rationale — Contemporary research has demonstrated that androgen-based pathways have a clinically significant role in the progression of castration-resistant prostate cancer. In addition to androgen production by the adrenal gland and testis, several of the enzymes involved in the synthesis of testosterone and dihydrotestosterone, including cytochrome P450 17-alpha-hydroxysteroid dehydrogenase (CYP17), are highly expressed in tumor tissue .
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- MOLECULAR PATHWAYS
- - Androgen synthesis inhibitors
- - Androgen receptor antagonists
- - Prior docetaxel chemotherapy
- - Chemotherapy-naïve patients
- - Prior enzalutamide therapy
- - Retreatment with abiraterone
- Clinical role
- ANDROGEN RECEPTOR ANTAGONISTS
- - Prior docetaxel chemotherapy
- - Chemotherapy-naïve patients
- - Prior abiraterone therapy
- Other androgen receptor antagonists
- COMBINING ABIRATERONE AND ENZALUTAMIDE
- SURVEILLANCE DURING TREATMENT
- SUMMARY AND RECOMMENDATIONS