Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Faculty of Medicine, Pharmacology, University of Helsinki, Helsinki, Finland.
BMJ Open. 2022 Apr 29;12(4):e050264. doi: 10.1136/bmjopen-2021-050264.
Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting.This study aims to test statins' efficacy compared to placebo in delaying development of CR during ADT treatment for primary metastatic or recurrent prostate cancer. Secondary aim is to explore effect of statin intervention on prostate cancer mortality and lipid metabolism during ADT.
In this randomised placebo-controlled trial, a total of 400 men with de novo metastatic prostate cancer or recurrent disease after primary treatment and starting ADT will be recruited and randomised 1:1 to use daily 80 mg of atorvastatin or placebo. All researchers, study nurses and patients will be blinded throughout the trial. Patients are followed until disease recurrence or death. Primary outcome is time to formation of CR after initiation of ADT. Serum lipid levels (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and trigyserides) are analysed to test whether changes in serum cholesterol parameters during ADT predict length of treatment response. Furthermore, the trial will compare quality of life, cardiovascular morbidity, changes in blood glucose and circulating cell-free DNA, and urine lipidome during trial.
This study is approved by the Regional ethics committees of the Pirkanmaa Hospital District, Science centre, Tampere, Finland (R18065M) and Tarto University Hospital, Tarto, Estonia (319/T-6). All participants read and sign informed consent form before study entry. After publication of results for the primary endpoints, anonymised summary metadata and statistical code will be made openly available. The data will not include any information that could make it possible to identify a given participant.
Clinicaltrial.gov: NCT04026230, Eudra-CT: 2016-004774-17, protocol code: ESTO2, protocol date 10 September 2020 and version 6.
血液胆固醇可能是前列腺癌预后的一个风险因素，而使用他汀类药物与降低前列腺癌复发和进展的风险有关。此外，使用他汀类药物与雄激素剥夺治疗（ADT）期间发生去势抵抗（CR）的时间延长有关。然而，他汀类药物在随机安慰剂对照研究中对延迟去势抵抗的疗效尚未得到验证。本研究旨在测试他汀类药物与安慰剂相比，在 ADT 治疗新发转移性或复发性前列腺癌时对 CR 发展的疗效。次要目的是探索他汀类药物干预对 ADT 期间前列腺癌死亡率和脂代谢的影响。
在这项随机安慰剂对照试验中，共招募了 400 名新诊断为转移性前列腺癌或原发性治疗后复发并开始 ADT 的患者，将其 1:1 随机分为每天服用 80mg 阿托伐他汀或安慰剂。所有研究人员、研究护士和患者在整个试验过程中均处于盲态。患者随访至疾病复发或死亡。主要结局是 ADT 开始后形成 CR 的时间。分析血清脂质水平（总胆固醇、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）和甘油三酯），以检测 ADT 期间血清胆固醇参数的变化是否预测治疗反应的持续时间。此外，该试验将比较试验期间的生活质量、心血管发病率、血糖和循环游离 DNA 的变化，以及尿液脂质组。
该研究已获得芬兰皮卡拉马医院区科学中心（R18065M）和爱沙尼亚塔尔图大学医院（Tarto，Estonia）（319/T-6）的区域伦理委员会批准。所有参与者在研究入组前阅读并签署知情同意书。主要终点结果公布后，将公开提供匿名汇总元数据和统计代码。数据将不包含任何可识别特定参与者的信息。
Clinicaltrial.gov：NCT04026230，Eudra-CT：2016-004774-17，方案代码：ESTO2，方案日期 2020 年 9 月 10 日，版本 6。
