Alternative endocrine therapies for castration-resistant prostate cancer
- Nancy A Dawson, MD
Nancy A Dawson, MD
- Professor of Medicine
- Lombardi Comprehensive Cancer Center
- Georgetown University
- Section Editors
- Nicholas Vogelzang, MD
Nicholas Vogelzang, MD
- Section Editor — Prostate Cancer
- Professor of Medicine
- University of Nevada School of Medicine
- US Oncology Research
- W Robert Lee, MD, MS, MEd
W Robert Lee, MD, MS, MEd
- Section Editor — Prostate Cancer
- Professor of Radiation Oncology
- Duke University Medical Center
- 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
Androgen deprivation therapy (ADT) is generally the initial treatment for men with advanced prostate cancer, either alone or in combination with chemotherapy. Standard approaches to the initial treatment with ADT include orchiectomy, a gonadotropin-releasing hormone (GnRH) agonist, or a combination of a GnRH agonist plus an antiandrogen (combined androgen blockade).
Despite initial response rates of 80 to 90 percent, nearly all men eventually develop castration-resistant disease. Patients who develop progressive disease after their initial ADT are considered to have castration-resistant prostate cancer (CRPC), although their disease may respond to secondary endocrine therapies. In this setting, two new agents, abiraterone and enzalutamide, have been shown to prolong overall survival and are the preferred systemic therapy when endocrine therapy is indicated (table 1). (See "Castration-resistant prostate cancer: Treatments targeting the androgen pathway", section on 'Abiraterone' and "Castration-resistant prostate cancer: Treatments targeting the androgen pathway", section on 'Enzalutamide'.)
Several alternative endocrine approaches (other older antiandrogens, antiandrogen withdrawal, ketoconazole, glucocorticoids, megestrol acetate, estrogens) appear to be less effective and have not been demonstrated to improve survival. However, these approaches may induce clinical responses or stable disease. These alternative endocrine therapies are often used sequentially and may be useful in postponing interventions such as chemotherapy, with its associated toxicity, or after chemotherapy when no other effective options are available.
These alternative endocrine approaches are discussed in this topic.
Overviews of the management of advanced castration-sensitive prostate cancer and CRPC are presented separately. (See "Overview of the treatment of disseminated castration-sensitive prostate cancer" and "Overview of the treatment of castration-resistant prostate cancer (CRPC)".)
- Virgo KS, Basch E, Loblaw DA, et al. Second-Line Hormonal Therapy for Men With Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion. J Clin Oncol 2017; :JCO2017728030.
- Suzuki H, Okihara K, Miyake H, et al. Alternative nonsteroidal antiandrogen therapy for advanced prostate cancer that relapsed after initial maximum androgen blockade. J Urol 2008; 180:921.
- Scher HI, Liebertz C, Kelly WK, et al. Bicalutamide for advanced prostate cancer: the natural versus treated history of disease. J Clin Oncol 1997; 15:2928.
- Joyce R, Fenton MA, Rode P, et al. High dose bicalutamide for androgen independent prostate cancer: effect of prior hormonal therapy. J Urol 1998; 159:149.
- Kucuk O, Fisher E, Moinpour CM, et al. Phase II trial of bicalutamide in patients with advanced prostate cancer in whom conventional hormonal therapy failed: a Southwest Oncology Group study (SWOG 9235). Urology 2001; 58:53.
- Penson DF, Armstrong AJ, Concepcion R, et al. Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial. J Clin Oncol 2016; 34:2098.
- Shore ND, Chowdhury S, Villers A, et al. Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol 2016.
- Decensi AU, Boccardo F, Guarneri D, et al. Monotherapy with nilutamide, a pure nonsteroidal antiandrogen, in untreated patients with metastatic carcinoma of the prostate. The Italian Prostatic Cancer Project. J Urol 1991; 146:377.
- Pfitzenmeyer P, Foucher P, Piard F, et al. Nilutamide pneumonitis: a report on eight patients. Thorax 1992; 47:622.
- Davis NB, Ryan CW, Stadler WM, Vogelzang NJ. A phase II study of nilutamide in men with prostate cancer after the failure of flutamide or bicalutamide therapy. BJU Int 2005; 96:787.
- Kassouf W, Tanguay S, Aprikian AG. Nilutamide as second line hormone therapy for prostate cancer after androgen ablation fails. J Urol 2003; 169:1742.
- Wysowski DK, Fourcroy JL. Flutamide hepatotoxicity. J Urol 1996; 155:209.
- Wysowski DK, Freiman JP, Tourtelot JB, Horton ML 3rd. Fatal and nonfatal hepatotoxicity associated with flutamide. Ann Intern Med 1993; 118:860.
- Fosså SD, Slee PH, Brausi M, et al. Flutamide versus prednisone in patients with prostate cancer symptomatically progressing after androgen-ablative therapy: a phase III study of the European organization for research and treatment of cancer genitourinary group. J Clin Oncol 2001; 19:62.
- Schröder FH, Collette L, de Reijke TM, Whelan P. Prostate cancer treated by anti-androgens: is sexual function preserved? EORTC Genitourinary Group. European Organization for Research and Treatment of Cancer. Br J Cancer 2000; 82:283.
- Small EJ, Halabi S, Dawson NA, et al. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol 2004; 22:1025.
- Sartor AO, Tangen CM, Hussain MH, et al. Antiandrogen withdrawal in castrate-refractory prostate cancer: a Southwest Oncology Group trial (SWOG 9426). Cancer 2008; 112:2393.
- Caffo O, Palermo A, Veccia A, et al. Biochemical and objective response to abiraterone acetate withdrawal: incidence and clinical relevance of a new scenario for castration-resistant prostate cancer. Urology 2013; 82:1090.
- Eisenberger MA, Blumenstein BA, Crawford ED, et al. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med 1998; 339:1036.
- Eichenberger T, Trachtenberg J, Toor P, Keating A. Ketoconazole: a possible direct cytotoxic effect on prostate carcinoma cells. J Urol 1989; 141:190.
- Blum RA, D'Andrea DT, Florentino BM, et al. Increased gastric pH and the bioavailability of fluconazole and ketoconazole. Ann Intern Med 1991; 114:755.
- Nishimura K, Nonomura N, Satoh E, et al. Potential mechanism for the effects of dexamethasone on growth of androgen-independent prostate cancer. J Natl Cancer Inst 2001; 93:1739.
- Fakih M, Johnson CS, Trump DL. Glucocorticoids and treatment of prostate cancer: a preclinical and clinical review. Urology 2002; 60:553.
- Yano A, Fujii Y, Iwai A, et al. Glucocorticoids suppress tumor angiogenesis and in vivo growth of prostate cancer cells. Clin Cancer Res 2006; 12:3003.
- Yano A, Fujii Y, Iwai A, et al. Glucocorticoids suppress tumor lymphangiogenesis of prostate cancer cells. Clin Cancer Res 2006; 12:6012.
- Venkitaraman R, Lorente D, Murthy V, et al. A randomised phase 2 trial of dexamethasone versus prednisolone in castration-resistant prostate cancer. Eur Urol 2015; 67:673.
- Small EJ, Meyer M, Marshall ME, et al. Suramin therapy for patients with symptomatic hormone-refractory prostate cancer: results of a randomized phase III trial comparing suramin plus hydrocortisone to placebo plus hydrocortisone. J Clin Oncol 2000; 18:1440.
- Kantoff PW, Halabi S, Conaway M, et al. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study. J Clin Oncol 1999; 17:2506.
- Geller J, Albert J, Geller S, et al. Effect of megestrol acetate (Megace) on steroid metabolism and steroid-protein binding in the human prostate. J Clin Endocrinol Metab 1976; 43:1000.
- Leinung MC, Liporace R, Miller CH. Induction of adrenal suppression by megestrol acetate in patients with AIDS. Ann Intern Med 1995; 122:843.
- Landström M, Damber JE, Bergh A. Estrogen treatment postpones the castration-induced dedifferentiation of Dunning R3327-PAP prostatic adenocarcinoma. Prostate 1994; 25:10.
- Manikandan R, Srirangam SJ, Pearson E, et al. Diethylstilboestrol versus bicalutamide in hormone refractory prostate carcinoma: a prospective randomized trial. Urol Int 2005; 75:217.
- CONTINUATION OF ADT
- ANTIANDROGENS AND ANTIANDROGEN WITHDRAWAL
- - Bicalutamide
- - Nilutamide
- - Flutamide
- - Cyproterone acetate
- Antiandrogen withdrawal
- OTHER AGENTS
- Megestrol acetate
- SURVEILLANCE DURING TREATMENT
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS