Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
CRUK Beatson Institute, Glasgow, UK.
BJU Int. 2023 Feb;131(2):236-243. doi: 10.1111/bju.15851. Epub 2022 Aug 12.
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.
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 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 .
At 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.
Data 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.
检测他汀类药物对去势抵抗性前列腺癌（CRPC）患者的作用证据，因为前列腺癌患者诊断后使用他汀类药物与有利的生存结果相关。
SPECTRE 试验是一项为期 6 周的概念验证性单臂 II 期治疗试验，联合阿托伐他汀和雄激素剥夺疗法治疗 CRPC 患者（无论转移状态如何），旨在检测他汀类药物对 CRPC 患者的作用证据。主要研究终点是在阿托伐他汀治疗期间的任何时间内，从基线水平下降≥50%的前列腺特异性抗原（PSA）水平的患者比例（PSA 反应）。探索性终点包括 PSA 速度和通过质谱法鉴定的血清代谢物。
在预定的中期分析中，12 名患者中有 1 名（主要终点）经历了 PSA 水平下降≥50%，需要至少 2 名患者满足主要终点才能进一步招募。所有 12 名患者在他汀类药物治疗后均经历了血清胆固醇水平的大幅下降。虽然所有患者的 PSA 速度在研究前均相似，但 12 名患者中有 6 名在他汀类药物治疗后 PSA 速度下降，提示疾病稳定。对每周连续血样进行无偏代谢组学分析表明，色氨酸是与患者对他汀类药物反应相关的主要代谢物。
SPECTRE 研究的数据首次提供了他汀类药物对 CRPC 的作用证据，并早期提示疾病稳定。我们的数据还强调了改变色氨酸代谢与肿瘤反应相关的可能性。
