A phase II study of atorvastatin and celecoxib in patients with rising PSA following local therapy for prostate cancer (PC).

Abstract

89 Background: Single agent atorvastatin and celecoxib have been associated with reductions in the risk of PC. Our laboratories have demonstrated that low doses of the drug combination have synergistic effects inhibiting the progression of LNCaP tumors to androgen independence. We therefore sought to determine the effects of the combination in androgen-dependent PC on PSA kinetics and the plasma correlates of IL-6, C-reactive protein (CRP), PGE-2, and the pharmacokinetics of the drug combination to validate preclinical biomarker findings. Methods: Patients with rising PSA after primary therapy for PC were enrolled. Patient must have three rising PSA values, each obtained at least 1 month apart. No prior hormone-ablative therapy was allowed, except in the neoadjuvant setting or in the setting of salvage XRT completed 3 months prior to enrollment. Patients with any history of coronary artery disease or a previous myocardial infarction in the past 6 months were excluded. All patients were treated with atorvastatin 20 mg daily and celecoxib 200 mg twice a day for 6 months. Paired pre-treatment and on treatment PSA kinetics were compared using the Wilcoxon Signed Rank test. Results: We report on 14 patients that have completed therapy. Median pretreatment PSA slope was 0.14 log PSA/mo (median PSADT 4.98 mos), in contrast to the median on treatment slope of 0.09 log PSA/mo (median PSADT 7.37 mos); p=0.11. Eleven of the fourteen patients completed the 6 months of therapy, 1 patient withdrew and 2 patients therapy was stopped early due to lack of response. A declining PSA was observed in one patient. The combination was well tolerated, with no clinically significant therapy related toxicities ( > grade 1) reported in 76 months of therapy. Conclusions: In this ongoing phase II trial, the combination of low dose atorvastatin and celecoxib has been well tolerated and demonstrates a tendency of increasing PSA doubling time. Enrollment continues with analysis of IL-6, CRP, and PGE-2 to be correlated to individual clinical results.