Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
J Sex Med. 2018 Sep;15(9):1293-1299. doi: 10.1016/j.jsxm.2018.07.009.
Radical prostatectomy (RP) is associated with erectile dysfunction, largely mediated through cavernous nerve injury. There are robust pre-clinical data supporting a potential role for neuromodulatory agents in this patient population. This study assessed tacrolimus in improving erectile function recovery rates after RP (ClinicalTrials.gov number, NCT00106392).
To define the utility of oral tacrolimus in improving erectile function recovery after nerve sparing radical prostatectomy.
A randomized, double-blind trial compared tacrolimus 2-3 mg daily and placebo in men undergoing RP. Patients had localized prostate cancer and excellent baseline erectile function, underwent bilateral nerve-sparing RP, and were followed up for at least 18 months after RP. Patients received study drug for 27 weeks and completed the International Index of Erectile Function erectile function domain (EFD) questionnaire at baseline and serially after surgery.
International Index of Erectile Function erectile function domain score.
Data were available for 124 patients (59 tacrolimus, 65 placebo); mean age was 54.6 ± 6.2 years. No patient experienced permanent creatinine or potassium elevation. At baseline, mean EFD scores were 28.6 ± 2.1 (tacrolimus group) and 29 ± 1.5 (placebo group). By week 5, mean EFD scores had dropped to 8 ± 9.4 (tacrolimus) and 9 ± 10.7 (placebo). At 18 months, mean EFD scores were 16.0 ± 11.3 (tacrolimus) and 20.2 ± 9.0 (placebo) (P = .09). Tacrolimus failed to meet significance (hazard ratio = 0.83; P = .50), with no difference in: (i) percentage of patients achieving normal spontaneous erectile function (EFD score ≥24), (ii) time to normalization of EFD score (≥24), (iii) percentage of patients capable of intercourse in response to phosphieserase type 5 inhibitor (PDE5i), and (iv) time to achieve response to PDE5i.
Despite positive animal data, oral tacrolimus as used in this trial failed to improve erectile function after nerve sparing radical prostatectomy.
STRENGTHS & LIMITATIONS: The study is limited by a high attrition rate. The strengths include a randomized, placebo controlled design, extensive patient monitoring, use of medication diaries and a validated instrument as the primary outcome measure.
Despite supportive animal data, tacrolimus used in this fashion in the RP population failed to demonstrate any superiority over placebo. Mulhall JP, Klein EA, Slawin K, et al. A Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Utility of Tacrolimus (FK506) for the Prevention of Erectile Dysfunction Following Bilateral Nerve-Sparing Radical Prostatectomy. J Sex Med 2018;15:1293-1299.
根治性前列腺切除术（RP）与勃起功能障碍有关，主要通过海绵体神经损伤介导。有大量的临床前数据支持神经调节药物在这一患者群体中的潜在作用。本研究评估了他克莫司在改善接受神经保留性前列腺切除术（RP）后的勃起功能恢复率方面的作用（临床试验.gov 编号：NCT00106392）。
确定口服他克莫司在改善神经保留性前列腺切除术后勃起功能恢复中的作用。
一项随机、双盲试验比较了他克莫司 2-3 毫克/天和安慰剂在接受 RP 的男性中的应用。患者患有局限性前列腺癌，且勃起功能基线良好，接受双侧神经保留性 RP 治疗，并在 RP 后至少 18 个月接受随访。患者接受研究药物治疗 27 周，并在基线和手术后连续完成国际勃起功能指数（EFD）问卷的勃起功能域（EFD）部分。
国际勃起功能指数（EFD）勃起功能域评分。
124 例患者（他克莫司 59 例，安慰剂 65 例）的数据可用；平均年龄为 54.6±6.2 岁。无患者出现永久性肌酐或钾升高。基线时，EFD 评分平均为 28.6±2.1（他克莫司组）和 29±1.5（安慰剂组）。第 5 周时，EFD 评分分别降至 8±9.4（他克莫司）和 9±10.7（安慰剂）。18 个月时，EFD 评分分别为 16.0±11.3（他克莫司）和 20.2±9.0（安慰剂）（P=0.09）。他克莫司未达到显著性（风险比=0.83；P=0.50），在以下方面没有差异：（i）达到正常自发勃起功能（EFD 评分≥24）的患者比例，（ii）EFD 评分正常化的时间（≥24），（iii）对磷酸二酯酶 5 抑制剂（PDE5i）有反应的患者比例，以及（iv）达到 PDE5i 反应的时间。
尽管有阳性的动物数据，但本试验中使用的口服他克莫司未能改善神经保留性根治性前列腺切除术后的勃起功能。
研究受到高失访率的限制。其优点包括随机、安慰剂对照设计、对患者的广泛监测、使用药物日记和验证工具作为主要的结果测量。
尽管有支持性的动物数据，但在 RP 人群中以这种方式使用他克莫司并没有显示出比安慰剂更优越的效果。Mulhall JP、Klein EA、Slawin K 等。一项随机、双盲、安慰剂对照试验，评估他克莫司（FK506）在预防双侧神经保留性根治性前列腺切除术后勃起功能障碍中的作用。J 性医学 2018；15：1293-1299。
