Department of Surgery, McGill University, Montreal, Quebec, Canada.
J Urol. 2013 Apr;189(4):1421-6. doi: 10.1016/j.juro.2012.11.003. Epub 2012 Nov 7.
We conducted a safety and efficacy evaluation of intraprostatic injection of PRX302, a modified pore forming protein (proaerolysin) activated by prostate specific antigen, as a highly targeted, localized approach to treat lower urinary tract symptoms due to benign prostatic hyperplasia.
A total of 92 patients with I-PSS (International Prostate Symptom Score) 15 or greater, peak urine flow 12 ml or less per second and prostate volume 30 to 100 ml were randomized 2:1 to a single ultrasound guided intraprostatic injection of PRX302 vs vehicle (placebo) in this phase IIb double-blind study. Injection was 20% of prostate volume and 0.6 μg PRX302 per gm prostate. Peak urine flow was determined by a blinded reviewer. Benign prostatic hyperplasia medications were prohibited. The primary data set of efficacy evaluable patients (73) was analyzed using last observation carried forward.
PRX302 treatment resulted in an approximate 9-point reduction in I-PSS and 3 ml per second increase in peak urine flow that were statistically significant changes from baseline compared to vehicle. Efficacy was sustained for 12 months. Early withdrawal for other benign prostatic hyperplasia treatment was more common for patients in the vehicle group. Relative to vehicle, PRX302 apparent toxicity was mild, transient, and limited to local discomfort/pain and irritative urinary symptoms occurring in the first few days, with no effect on erectile function.
A single administration of PRX302 as a short, outpatient based procedure was well tolerated in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. PRX302 produced clinically meaningful and statistically significant improvement in patient subjective (I-PSS) and quantitative objective (peak urine flow) measures sustained for 12 months. The side effect profile is favorable with most effects attributed to the injection itself and not related to drug toxicity.
我们评估了经直肠前列腺内注射 PRX302 的安全性和疗效，PRX302 是一种经前列腺特异抗原激活的改良孔形成蛋白（原 aerolysin），是一种高度靶向、局部的方法，用于治疗良性前列腺增生引起的下尿路症状。
本 IIb 期双盲研究共纳入 92 例 I-PSS（国际前列腺症状评分）≥15 分、最大尿流率＜12ml/s 且前列腺体积 30-100ml 的患者，按 2:1 的比例随机分为经直肠超声引导下前列腺内注射 PRX302 组（20%前列腺体积，0.6μg PRX302/gm 前列腺）和安慰剂组。最大尿流率由盲法评价者评估。治疗期间禁止使用治疗良性前列腺增生的药物。采用意向性治疗分析（ITT）集（可评估疗效的 73 例患者）分析主要疗效终点。
与安慰剂组相比，PRX302 治疗后 I-PSS 评分平均降低约 9 分，最大尿流率平均增加 3ml/s，差异均具有统计学意义。疗效持续 12 个月。与安慰剂组相比，因其他良性前列腺增生治疗而早期退出的患者更多。与安慰剂组相比，PRX302 组不良反应轻微、短暂，仅限于注射后最初几天出现局部不适/疼痛和刺激性尿路症状，不影响勃起功能。
对于良性前列腺增生所致下尿路症状患者，单次 PRX302 经直肠前列腺内注射治疗是安全耐受的。PRX302 治疗可显著改善患者的主观（I-PSS）和客观（最大尿流率）指标，疗效持续 12 个月，且具有临床意义。不良反应谱良好，大多数不良反应与注射本身相关，与药物毒性无关。
