ASCO GU 2008 - Secondary Androgen Deprivation: Treating The Prostate Specific Antigen Or The Patient

Main Category: Prostate / Prostate Cancer
Also Included In: Endocrinology;  Men's health
Article Date: 17 Feb 2008 - 0:00 PDT

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UroToday.com - Dr. Oh reviewed the past and present of secondary hormonal therapies. He showed patient cases of sequential secondary therapies with outcomes supporting the heterogeneity of CaP. Some patients metastasize then develop castration resistant prostate cancer (CRPC) while others have CRPC when metastases occur, perhaps due to the increased early use of androgen deprivation therapy. In some patients, rapid progression supports the direct use of chemotherapy without secondary hormonal therapy. He asked whether secondary hormonal therapies are effective. About 25% of patients had a major PSA decline after stopping flutamide and has subsequently been described with other anti-androgens. However, in a large CALBG trail the flutamide withdrawal response was only 11%. AR mutations do not explain the anti-androgen withdrawal response, with only 10% of bone biopsies showing a mutation. None of the secondary hormonal therapies have shown survival benefit, but some show PSA response (>50% decline in the PSA). High dose bicalutamide showed a 20-24% PSA response rate. Nilutamide showed a 29-50% response rate, perhaps reflecting different mechanisms. While these agents are oral with few side effects, they are expensive with relatively low response rates.

Low dose corticosteroids demonstrate an 18-22% PSA response rate and a pain response rate of 12-38%. Yet the duration of response is short. Ketoconazole and hydrocortisone show a 27-63% PSA response rate. Baseline adrenal androgen levels do go down one month after ketokonazole, but increase when disease recurs. Ketoconazole is metabolized by CYP3A4 and thus its use can interfere with metabolism of other drugs. DES provides a response in about 25% of patients at a dose of 1.25mg TID. The pulmonary embolism/deep venous thrombosis rate was 7%.

He concluded that secondary hormonal therapies are effective for some patients, but the data is anecdotal. PSA may be a valid endpoint for screening new drugs, but does not replace survival or QOL. Finally, there is a need to identify patients for whom secondary hormonal therapy may be useful, such as increased adrenal activity or greater AR signaling.

Presented by William K. Oh at the American Society of Clinical Oncology (ASCO) - 2008 Genitourinary Cancers Symposium - A Multidisciplinary Approach - February 14-16, 2008 San Francisco, California, USA

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS Professor & Chairman Department of Urology University of California, Davis, School of Medicine Sacramento, CA

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