Phase II proof of concept study of atorvastatin in castration resistant prostate cancer

Objectives:\ud To test for evidence of statin-mediated effects in patients with castration resistant prostate cancer as post-diagnosis use of statins in patients with prostate cancer is associated with favourable survival outcome. Enhanced tumoral cholesterol uptake can drive castration resistant prostate cancer (CRPC). However, it remains unclear whether these associations result from confounding factors or directly from statin mediated effects.\ud \ud Patients and Methods:\ud The SPECTRE trial was a 6-weeks long proof-of-concept single-arm Phase II treatment trial combining atorvastatin and androgen deprivation therapy in patients with CRPC (regardless of the metastatic status), designed to test for evidence of statin-mediated effects in patients with CRPC. The primary study endpoint was the proportion of patients achieving ≥50% drop from baseline in PSA levels at any time over the 6-week period of atorvastatin medication (PSA response). Exploratory endpoints include PSA velocity and mass spectrometrically identified serum metabolites.\ud \ud Results:\ud At scheduled interim analysis, one of twelve patients experienced a ≥50% drop in PSA levels (primary endpoint), with ≥2 patients satisfying the primary endpoint required for further recruitment. All 12 experienced substantial falls in serum cholesterol levels following statin treatment. While all patients had comparable pre-study PSA velocities, 6 of 12 patients showed decreased PSA velocities following statin treatment, suggestive of disease stablisation. Unbiased metabolomics analysis on serial weekly blood samples identified tryptophan to be the dominant metabolite associated with patient response to statin.\ud \ud Conclusions:\ud Data from the SPECTRE study provides the first evidence of statin mediated effects on CRPC and early sign of disease stabilisation. Our data also highlights the possibility of altered tryptophan metabolism being associated with tumour response.