Prostatic Neoplasms
Conditions
Keywords
Apoptosis, Atorvastatin, Inflammation, Pre-surgical trial, Proliferation, Prostate cancer
Brief summary
This single-center, randomized, double-blind trial assesses the impact of short-term atorvastatin administration on proliferation activity, apoptotic rate and histological inflammation in prostate tissue.
Detailed description
In this trial 160 men who have been diagnosed with prostate cancer, and whose first-line treatment will be radical prostatectomy (surgical removal of the prostate), are randomized to receive either 80 mg atorvastatin or placebo daily for 2-5 weeks until the operation. Blood cholesterol and serum PSA are measured before starting the study drug use and before the operation. After the operation change in PSA and histological inflammation, apoptotic rate and Ki-67 staining intensity are compared between atorvastatin-treated and placebo-treated men. The correlation between changes in serum cholesterol or prostate specific antigen (PSA) and the tissue characteristics is evaluated. After recruiting 60 men we will perform an interim analysis on primary end-points without breaking the blinding to treatment allocation. If we observe a statistically significant difference in all primary end-points, the trial will be stopped early and the results published. Additionally, atorvastatin concentration in the blood and the prostate tissue is measured with mass spectrometry to determine penetrance of atorvastatin into the prostate. DNA- and RNA-samples are obtained from the prostate tissue and the blood. These will be used to study how gene expression of statin- and cholesterol-modifying enzymes affects the responses observed in prostate tissue. As a secondary end-point we will measure recovery of erectile function after the operation and compare between the two study arms. Erectile function is measured using IIEF-5 questionnaire once before the operation and again 3, 6, 9 and 12 months from the prostatectomy.
Interventions
DRUGAtorvastatin
Capsules including 80 mg of atorvastatin
DRUGPlacebo
Similar capsules as in the atorvastatin arm, but without the active ingredient
Sponsors
Tampere University
Fimlab laboratories
University of Eastern Finland
Finnish Cultural Foundation
Tampere University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Prostate cancer proven histologically in prostate biopsy * Radical prostatectomy selected as the first-line treatment * Willingness to participate and sign informed consent
Exclusion criteria
* Previous oncological treatments for any malignancy * Previous usage of statins, finasteride or dutasteride within a year prior to prostate cancer diagnosis * Clinically significant liver- or kidney insufficiency (plasma alanine aminotransferase level is twice over the recommended upper limit or serum creatinine level is over 170 µmol/l) * Previous adverse effects from cholesterol-lowering treatment * Ongoing use of drugs having interactions with statins (St John's Wort, HIV protease inhibitors, ciclosporin, macrolide antibiotics, fusidic acid, phenytoin, carbamazepine, dronedarone or oral antifungal medication)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ki-67 expression | Four weeks after recruitment | Cellular proliferation activity in prostate tissue as measured by Ki-67 expression. Measured after radical prostatectomy, on average after 4 weeks of recruitment |
| Apoptosis | Four weeks after recruitment | Number of apoptotic cells in prostate tissue. Measured after radical prostatectomy, on average after 4 weeks of recruitment |
| Histological inflammation | After prostatectomy | Extent of histological inflammation in the prostate tissue as evaluated by study pathologist |
| serum PSA | At recruitment and before prostatectomy | Change in serum PSA level as measured before starting the study drug and again just before prostatectomy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Atorvastatin level in prostate tissue | Four weeks after recruitment | Measurement of atorvastatin level in prostate tissue with mass spectrometry. Measured after radical prostatectomy, on average four weeks after recruitment |
| serum cholesterol | At recruitment and again four weeks after | Changes in measured fasting serum cholesterol parameters: total cholesterol, HDL and LDL. First measure is done at recruitment, another right before radical prostatectomy. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Genotype of cholesterol-metabolizing enzymes | Post-hoc analysis, one year after recruitment completes | Genotyping of cholesterol-metabolizing enzymes from blood and tissue samples |
| Erection function | One year after prostatectomy | Erectile function as measured with IIEF-5 questionnaire before prostatectomy and again at 3 month intervals during the first year after prostatectomy |
| Genotype of statin-metabolizing enzymes | Post hoc analysis, one year after recruitment completes | Genotyping statin-metabolizing enzymes from blood and tissue samples |
Countries
Finland
Outcome results
None listed