Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Eur Urol. 2011 May;59(5):747-54. doi: 10.1016/j.eururo.2010.11.024. Epub 2010 Nov 24.
PRX302 is a prostate specific antigen (PSA)-activated pore-forming protein toxin under development as a targeted approach for improving lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) without affecting sexual function.
To evaluate the safety and efficacy of PRX302 in men with moderate to severe BPH.
DESIGN, SETTING, AND PARTICIPANTS: Eligible subjects were refractory, intolerant, or unwilling to undergo medical therapies for BPH and had International Prostate Symptom Score (IPSS) ≥12, a quality of life (QoL) score ≥3, and prostate volumes between 30 and 80 g. Fifteen patients were enrolled in phase 1 studies, and 18 patients entered phase 2 studies.
Subjects received intraprostatic injection of PRX302 into the right and left transition zone via a transperineal approach in an office-based setting. Phase 1 subjects received increasing concentrations of PRX302 at a fixed volume; phase 2 subjects received increasing volumes per deposit at a fixed concentration.
IPSS, QoL, prostate volume, maximum flow rate (Q(max)), International Index of Erectile Function, serum PSA levels, pharmacokinetics, and adverse events were recorded at 30, 60, 90, 180, 270, and 360 d after treatment with PRX302.
Sixty percent of men in the phase 1 study and 64% of men in the phase 2 study treated with PRX302 had ≥30% improvement compared to baseline in IPSS out to day 360. Patients also experienced improvement in QoL and reduction in prostate volume out to day 360. Patients receiving ≥1 ml of PRX302 per deposit had the best response overall. PRX302 had no deleterious effect on erectile function. Adverse events were mild to moderate and transient in nature. The major study limitation was the small sample size.
The promising safety profile and evidence of efficacy in the majority of treated subjects in these phase 1 and 2 studies supports further development of PRX302 as a minimally invasive, targeted treatment for BPH.
PRX302 是一种前列腺特异性抗原（PSA）激活的孔形成蛋白毒素，作为一种针对良性前列腺增生（BPH）的靶向治疗方法正在开发中，可改善由 BPH 引起的下尿路症状（LUTS），而不影响性功能。
评估 PRX302 在中重度 BPH 男性中的安全性和疗效。
设计、地点和参与者：合格的受试者对 BPH 的药物治疗有耐药性、不耐受或不愿意接受治疗，国际前列腺症状评分（IPSS）≥12，生活质量（QoL）评分≥3，前列腺体积在 30 到 80 克之间。15 名患者参加了 1 期研究，18 名患者参加了 2 期研究。
受试者通过经会阴途径在办公室环境下接受经前列腺内注射 PRX302 到右侧和左侧移行区。1 期受试者接受递增浓度的 PRX302 固定体积；2 期受试者接受递增体积/沉积固定浓度。
在 PRX302 治疗后 30、60、90、180、270 和 360 天，记录 IPSS、QoL、前列腺体积、最大尿流率（Q(max)）、国际勃起功能指数、血清 PSA 水平、药代动力学和不良事件。
1 期研究中 60%的男性和 2 期研究中 64%的男性在 PRX302 治疗后至 360 天，与基线相比，IPSS 有≥30%的改善。患者还在 QoL 方面有所改善，并在 360 天内降低了前列腺体积。接受≥1ml/沉积 PRX302 的患者总体反应最佳。PRX302 对勃起功能没有不良影响。不良事件为轻度至中度，且为一过性。主要研究局限性是样本量小。
这些 1 期和 2 期研究中大多数接受治疗的受试者的安全性和疗效具有令人鼓舞的前景，支持进一步开发 PRX302 作为一种微创、靶向治疗 BPH 的方法。
