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) is generally the initial treatment for men with metastatic prostate cancer. Standard approaches include bilateral orchiectomy or medical orchiectomy using a gonadotropin releasing hormone (GnRH) agonist either 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 castrate-resistant prostate cancer. Contemporary research in men with castrate-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 castrate resistant prostate cancer. These approaches are discussed here.
An overview of the management of advanced prostate cancer is presented separately. (See "Overview of the treatment of disseminated prostate cancer".)
Rationale — Contemporary research has demonstrated that androgen-based pathways continue to have a clinically significant role in the progression of castrate-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 naive patients
- - Prior enzalutamide therapy
- Clinical role
- Other androgen synthesis inhibitors
- Prior docetaxel chemotherapy
- Chemotherapy naive patients
- Prior abiraterone therapy
- COMBINING ABIRATERONE AND ENZALUTAMIDE
- SURVEILLANCE DURING TREATMENT
- SUMMARY AND RECOMMENDATIONS