Antiandrogen Withdrawal in Treating Patients With Hormone-Refractory Prostate Cancer

RATIONALE: Antiandrogen withdrawal may be an effective treatment for prostate cancer. PURPOSE: Randomized phase III trial to study the effectiveness of ketoconazole and hydrocortisone for antiandrogen withdrawal in treating men with prostate cancer that is refractory to hormone therapy.

Sex

Male

Maximum age

120 Years

DISEASE CHARACTERISTICS: Histologically diagnosed adenocarcinoma of the prostate Progressive metastatic or regional nodal disease after at least 4 weeks on flutamide, bicalutamide, or nilutamide, i.e.: Greater than 25% increase in sum of products of perpendicular diameters of all measurable lesions not previously irradiated OR Prostate-specific antigen (PSA) at least 5 ng/mL and risen from baseline on at least 2 successive occasions at least 2 weeks apart PSA progression required for "bone only" disease or disease that responded to androgen deprivation and is negative on imaging scans at entry Primary testicular androgen suppression with a luteinizing hormone-releasing hormone (LHRH) analogue plus antiandrogen or by orchiectomy required Intermittent LHRH analog/antiandrogen therapy resumed at least 4 weeks prior to and continued at time of entry LHRH analogue continued throughout study in absence of orchiectomy

PATIENT CHARACTERISTICS: Age: Any age Performance status: 0-2 Hematopoietic: Not specified Hepatic: Bilirubin no greater than 1.5 times normal AST no greater than 3 times normal Renal: Not specified Other: No active, uncontrolled condition including: Bacterial, viral, or fungal infection Hyperglycemia Gastric or duodenal ulcer No existing medical condition requiring systemic corticosteroids (inhaled and topical steroids allowed) No concurrent use of the following: Terfenadine Astemizole Cisapride

PRIOR CONCURRENT THERAPY: No prior therapy with experimental agents for metastatic disease Biologic therapy: No prior immunotherapy for metastatic disease Chemotherapy: No prior estramustine or other chemotherapy for metastatic disease Endocrine therapy: See Disease Characteristics No prior hormonal therapy for metastatic disease No prior aminoglutethimide No prior ketoconazole No prior hydrocortisone or other corticosteroids Prior experimental hormonal therapy requires approval of study chair Radiotherapy: At least 4 weeks since radiotherapy (8 weeks since strontium therapy) Surgery: Orchiectomy allowed

• BACKGROUNDD'Amico AV, Halabi S, Vogelzang NJ, et al.: A reduction in the rate of PSA rise following chemotherapy in patients with metastatic hormone refractory prostate cancer (HRPC) predicts survival: results of a pooled analysis of CALGB HRPC trials. [Abstract] J Clin Oncol 22 (Suppl 14): A-4506, 383s, 2004.
• BACKGROUNDHalabi S, Small EJ, Kantoff PW, Kattan MW, Kaplan EB, Dawson NA, Levine EG, Blumenstein BA, Vogelzang NJ. Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer. J Clin Oncol. 2003 Apr 1;21(7):1232-7. doi: 10.1200/JCO.2003.06.100. PMID 12663709
• BACKGROUNDGilligan TD, Halabi S, Kantoff PW, et al.: African-American race is associated with longer survival in patients with metastatic hormone-refractory prostate cancer (HRCaP) in four randomized phase III Cancer and Leukemia Group B (CALGB) trials. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-725, 2002.
• RESULTRyan CJ, Halabi S, Ou SS, Vogelzang NJ, Kantoff P, Small EJ. Adrenal androgen levels as predictors of outcome in prostate cancer patients treated with ketoconazole plus antiandrogen withdrawal: results from a cancer and leukemia group B study. Clin Cancer Res. 2007 Apr 1;13(7):2030-7. doi: 10.1158/1078-0432.CCR-06-2344. PMID 17404083
• RESULTRyan CJ, Halabi S, Kaplan E, et al.: Use of adrenal androgen levels to predict response to ketoconazole in patients with androgen independent prostate cancer: results from CALGB 9583. [Abstract] J Clin Oncol 22 (Suppl 14): A-4558, 396s, 2004.
• RESULTSmall EJ, Halabi S, Dawson NA, Stadler WM, Rini BI, Picus J, Gable P, Torti FM, Kaplan E, Vogelzang NJ. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol. 2004 Mar 15;22(6):1025-33. doi: 10.1200/JCO.2004.06.037. PMID 15020604
• RESULTHalabi S, Small EJ, Hayes DF, Vogelzang NJ, Kantoff PW. Prognostic significance of reverse transcriptase polymerase chain reaction for prostate-specific antigen in metastatic prostate cancer: a nested study within CALGB 9583. J Clin Oncol. 2003 Feb 1;21(3):490-5. doi: 10.1200/JCO.2003.04.104.