Prospective evaluation of atorvastatin in patients with PSA relapse after definitive treatment for prostate cancer

Abstract

1526 Background: The chemopreventive effect of statins in prostate cancer is controversial. There have been no prospective trials. As a prospective evaluation would represent a formidable task, we decided to conduct an exploratory evaluation of the effects of atorvastatin on the PSA level in patients with noncastrate, hormone naïve, isolated PSA relapses (biochemical failure) after initial definitive therapy. All known agents with potentially chemopreventive effect have historically demonstrated measurable activity in patients with early stages of neoplasia. Methods: Prospective, phase II, 2 stage study conducted at M. D. Anderson Cancer Center Orlando. Alpha =.05, Beta=.2. Stage I sample size: 10. Alternate hypothesis to be rejected if responses (R) are less or equal 1. Stage II sample size: 29. Alternate hypothesis to be rejected if R less or = 5. P0=0.10, P1=0.30. Primary Endpoint: PSA response after 6 months of therapy (decline of 50% or more). Eligibility: patients with prostate adenocarcinoma with PSA progression after either definitive radiation therapy or radical prostatectomy. Patients with PSA doubling time <3 months were excluded. Intervention: Atorvastatin 20mg/day by mouth for 6 months. Results: Eight patients have been accrued in the study so far. Median age: 73 [53 to 79]. One patient withdrew from the study after 5 months. No patients had evidence of metastases at study entry. Baseline median PSA was 2.65ng/mL [1.2 to 19.1ng/mL]. Median PSA at the end of study was 3.4ng/mL [1.5 to 33.9]. Median time to progression: 4 months. Responses: 0/8 Progressions: 5/8 Minor progressions: 2/8 No change: 1/8. No serious adverse events were reported. Conclusions: Even though this exploratory trial is ongoing, it is highly probable the alternative hypothesis will be rejected during the first stage. We have not observed any meaningful effect of atorvastatin at its most commonly used dose on PSA levels in patients with early -hormone naïve- biochemical failure after 6 months of therapy. This preliminary data does not support the potential use of atorvastatin as a chemopreventive agent. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer