Atorvastatin Before Prostatectomy and Prostate Cancer (ESTO1)

Tampere University Hospital

Status and phase

Completed

Phase 2

Conditions

Prostatic Neoplasms

Treatments

Drug: Placebo

Drug: Atorvastatin

Study type

Interventional

Funder types

Other

Identifiers

NCT01821404

2011-005438-20

Details and patient eligibility

About

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.

Full 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.

Enrollment

160 patients

Sex

Male

Ages

40 to 80 years old

Volunteers

No Healthy Volunteers

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)