A phase II study evaluating oral triamcinolone in patients with androgen independent prostate cancer

Abstract

4692 Background: As patients evolve from androgen-dependent to androgen independent prostate cancer (AIPC) some develop mutations in the androgen receptor (AR) allowing the cancer to grow in the absence of androgens. A double mutation in the ligand binding domain of the AR has been described in some patients with AIPC that renders the cancer responsive to corticosteroids including cortisol and cortisone. Preclinical studies demonstrated that, as opposed to cortisol, triamcinolone did not bind or activate the mutated AR. We therefore conducted a prospective trial for patients with AIPC with oral triamcinolone to suppress endogenous cortisol and evaluate response. Objective: To assess the serum prostate specific antigen (PSA) response and the time to progression in patients with AIPC treated with triamcinolone. Methods: Patients with AIPC and rising PSA who failed other therapies and were on androgen depletion therapy with castrate levels of testosterone were prospectively treated with oral triamcinolone acetonide 4 mg twice a day and were followed monthly with serum PSA and cortisol levels. Those patients who had a greater than 25% increase in serum PSA from baseline at 2 months were considered to have progressive disease and were removed from study. Those patients who had a fall in serum PSA or stable disease were continued until disease progression. Bone scans were obtained every 12 weeks and at progression. Results: Twenty four patients with AIPC were treated between 11/02 and 6/04. A partial response with a >50% fall in serum PSA was seen in 29%. Another 21% achieved stable disease for a total response rate of 50%. There was no statistically significant difference in time to progression in the partial responders and stable disease patients. The median time to progression was 7.5 months. Treatment was well tolerated without any grade 3 or 4 toxicities. Patients with a higher degree of cortisol suppression appeared to have a better serum PSA response than those patients whose cortisol was less suppressed. Conclusion: Oral triamcinolone was well tolerated in patients with AIPC and good responses in serum PSA were observed in 50% of subjects. No significant financial relationships to disclose.