Department of Surgery, Division of Urology University of Melbourne, Royal Melbourne Hospital, 5th Floor Clinical Sciences Building, Royal Parade, Parkville, Victoria 3050, Australia.
Br J Cancer. 2010 Aug 10;103(4):462-8. doi: 10.1038/sj.bjc.6605798. Epub 2010 Jul 20.
Angiogenesis is fundamental to the progression of many solid tumours including prostate cancer. Sodium selenate is a small, water-soluble, orally bioavailable activator of PP2A phosphatase with anti-angiogenic properties.
This was a dose-escalation phase I study in men with asymptomatic, chemotherapy-naïve, castration-resistant prostate cancer. The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included establishing the safety, tolerability and pharmacokinetic profile.
A total of 19 patients were enrolled. The MTD was 60 mg per day. Dose-limiting toxicity (fatigue and diarrhoea) was observed at 90 mg per day. The most frequently reported treatment-related adverse events across all treatment cohorts were nausea, diarrhoea, fatigue, muscle spasms, alopecia and nail disorders. No grade 4 toxicities were observed and there were no deaths on study. Linear pharmacokinetics was observed. One patient had a PSA response >50%. Median time to PSA progression (for non-responders) was 14.2 weeks. Mean PSA doubling time increased during the main treatment phase from 2.18 months before trial to 3.85 months.
Sodium selenate is well tolerated at a dose of 60 mg per day with modest single-agent efficacy similar to other anti-angiogenic agents. Further trials in combination with conventional cytotoxic regimens are warranted.
血管生成是许多实体瘤（包括前列腺癌）进展的基础。亚硒酸钠是一种具有抗血管生成特性的、小分子、水溶性、口服生物利用的 PP2A 磷酸酶激活剂。
这是一项在无症状、化疗初治、去势抵抗性前列腺癌男性中进行的剂量递增 I 期研究。主要目的是确定最大耐受剂量（MTD）。次要目标包括确定安全性、耐受性和药代动力学特征。
共纳入 19 例患者。MTD 为每天 60 毫克。每天 90 毫克时观察到剂量限制毒性（疲劳和腹泻）。所有治疗队列中最常报告的与治疗相关的不良事件是恶心、腹泻、疲劳、肌肉痉挛、脱发和指甲疾病。未观察到 4 级毒性，研究中无死亡。观察到线性药代动力学。1 例患者 PSA 反应>50%。非应答者的 PSA 进展中位时间为 14.2 周。在主要治疗阶段，PSA 倍增时间从试验前的 2.18 个月增加到 3.85 个月。
每天 60 毫克的亚硒酸钠耐受性良好，单药疗效适度，与其他抗血管生成药物相似。需要进一步进行联合常规细胞毒性方案的试验。
