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

Abstract

To test for evidence of statin-mediated effects in patients with castration-resistant prostate cancer (CRPC) as post-diagnosis use of statins in patients with prostate cancer is associated with favourable survival outcome. Patients and MethodsThe 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 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 a ≥50% drop from baseline in prostate-specific antigen (PSA) levels at any time over the 6-week period of atorvastatin medication (PSA response). Exploratory endpoints include PSA velocity and serum metabolites identified by mass spectrometry . ResultsAt the scheduled interim analysis, one of 12 patients experienced a ≥50% drop in PSA levels (primary endpoint), with ≥2 patients satisfying the primary endpoint required for further recruitment. All 12 patients experienced substantial falls in serum cholesterol levels following statin treatment. While all patients had comparable pre-study PSA velocities, six of 12 patients showed decreased PSA velocities after statin treatment, suggestive of disease stabilization. Unbiased metabolomics analysis on serial weekly blood samples identified tryptophan to be the dominant metabolite associated with patient response to statin. ConclusionsData from the SPECTRE study provide the first evidence of statin-mediated effects on CRPC and early sign of disease stabilization. Our data also highlight the possibility of altered tryptophan metabolism being associated with tumour response.

Don’t Judge a Book by Its Cover: The Role of Statins in Liver Cancer

“…The chemopreventive and cancer-treating effects of statins, which are the subject of this paper, are discussed in numerous research studies conducted in vitro, in vivo, and both as population-based observational studies and interventional clinical trials [29][30][31][32][33]. Research into the effects of statins used both in monotherapy and in combination with other drugs was investigated, obtaining many positive results.…”

Antidiabetics, Anthelmintics, Statins, and Beta-Blockers as Co-Adjuvant Drugs in Cancer Therapy

“…Half of the patients (6 out of 12 patients) presented a decrease in their PSA velocity with minimal side effects. The data are suggestive of disease stabilization following a short-course statin treatment [65]. The ongoing ESTO2 phase 3 randomized double-blind trial plans to enroll 400 patients with metastatic or recurrent prostate cancer to receive 80 mg daily atorvastatin vs. placebo during androgen-deprivation therapy.…”

“…Tumor growth delay in mice [27]; improved oxygenation in the prostatic tumor [4]; better oncological results in diabetic prostate cancer patients taking metformin [43] metformin and docetaxel for metastatic prostate cancer did not improve outcomes in nondiabetic patients [44] Synergistic effect with docetaxel increasing apoptosis and reducing tumor growth [88] ATV inhibited HIF-1α protein expression for increased radiosensitivity of prostate cancer cells [89]; atorvastatin and caffeine induced apoptotic death by downregulating phospho-Akt, phospho-Erk1/2,and anti-apoptotic Bcl-2 [90]; activation of LC3 transcription by atorvastatin induced autophagy in prostate cancer cells [91] Decreased PSA velocities after statin treatment in castration-resistant prostatic cancer patients [65] Cancer-specific mortality was found to be lower after the use of beta-blockers in observational studies [19]…”