Patel Hitendra R, Ilo Dapo, Shah Nimish, Cuzin Béatrice, Chadwick David, Andrianne Robert, Henneges Carsten, Barry Jane, Hell-Momeni Katja, Branicka Julia, Büttner Hartwig
Department of Urology, University Hospital North Norway, Sykehusvegen 38, 9038, Tromsø, Norway.
Lilly UK, Basingstoke, UK.
BMC Urol. 2015 Apr 12;15:31. doi: 10.1186/s12894-015-0022-9.
This multicenter, randomized, double-blind, double-dummy, placebo-controlled trial primarily evaluated the efficacy of tadalafil once-daily (OaD) or on-demand ("pro-re-nata"; PRN) treatment, started early post-nsRP. Secondary outcome-measures on quality-of-life (QoL) and treatment satisfaction are reported.
Patients, aged <68 yrs, with adenocarcinoma of the prostate (Gleason ≤ 7, normal preoperative erectile function [EF]) were randomized post-nsRP 1:1:1 to 9-month treatment with tadalafil 5 mg OaD, tadalafil 20 mg PRN, or placebo, followed by 6-week drug-free washout and 3-month open-label tadalafil OaD treatment (OLT). The main outcome measures were Changes in Expanded Prostate Cancer Index Composite (EPIC-26), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), and Self-Esteem and Relationship (SEAR) questionnaires (mixed-model-for-repeated-measures, including terms for treatment, visit, treatment-by-visit interaction, age-group, country, baseline-score). LS means with 95% confidence interval (CI) are reported.
423 patients were randomized to 3 treatment-groups: tadalafil OaD (N = 139), PRN (N = 143), or placebo (N = 141). In each group, 57 (41.0%), 58 (40.6%), and 50 (35.5%) patients were aged 61-68 yrs. At the end of double-blind treatment (DBT), patients' EPIC sexual domain-scores improved significantly with tadalafil OaD versus placebo (treatment effect [95% CI]: 9.6 [3.1,16.0]; p = 0.004); comparisons of PRN versus placebo at end of DBT, and comparisons of tadalafil OaD and PRN versus placebo after OLT were not significant. Only in older patients (61-68 yrs; age-by-treatment p ≤ 0.1), EPIC urinary incontinence domain-scores also improved significantly with tadalafil OaD versus placebo (overall treatment effect across all visits, 8.3 [0.4,16.1]; p = 0.040). Treatment satisfaction increased significantly in both tadalafil groups, EDITS total-scores increased significantly with OaD and PRN versus placebo during DBT (p = 0.005 and p = 0.041, respectively). At the end of OLT, improvement was significant for tadalafil OaD versus placebo only (p = 0.035). No significant differences were observed for SEAR.
These results suggest that chronic dosing of tadalafil improves QoL of patients post-nsRP. The improvement of urinary incontinence in elderly patients randomized to tadalafil OaD may contribute to this effect.
www.clinicaltrials.gov , NCT01026818.
这项多中心、随机、双盲、双模拟、安慰剂对照试验主要评估了他达拉非每日一次（OaD）或按需（“必要时”；PRN）治疗在nsRP术后早期开始使用的疗效。报告了生活质量（QoL）和治疗满意度的次要结局指标。
年龄<68岁、患有前列腺腺癌（ Gleason评分≤7，术前勃起功能[EF]正常）的患者在nsRP术后按1:1:1随机分为三组，分别接受9个月的5 mg他达拉非OaD治疗、20 mg他达拉非PRN治疗或安慰剂治疗，随后进行6周的药物洗脱期和3个月的开放标签他达拉非OaD治疗（OLT）。主要结局指标为前列腺癌指数综合扩展版（EPIC - 26）、治疗满意度勃起功能障碍量表（EDITS）以及自尊与关系（SEAR）问卷的变化（重复测量混合模型，包括治疗、访视、治疗×访视交互作用、年龄组、国家、基线评分等项）。报告了具有95%置信区间（CI）的最小二乘均值。
423例患者被随机分为3个治疗组：他达拉非OaD组（N = 139）、PRN组（N = 143）或安慰剂组（N = 141）。每组中，分别有57例（41.0%）、58例（40.6%）和50例（35.5%）患者年龄在61 - 68岁。在双盲治疗（DBT）结束时，与安慰剂相比，他达拉非OaD组患者的EPIC性功能领域评分显著改善（治疗效果[95%CI]：9.6 [3.1, 16.0]；p = 0.004）；DBT结束时PRN组与安慰剂组的比较，以及OLT后他达拉非OaD组和PRN组与安慰剂组的比较均无显著差异。仅在老年患者（61 - 68岁；年龄×治疗p≤0.1）中，与安慰剂相比，他达拉非OaD组的EPIC尿失禁领域评分也显著改善（所有访视的总体治疗效果，8.3 [0.4, 16.1]；p = 0.040）。两个他达拉非组的治疗满意度均显著提高，DBT期间OaD组和PRN组的EDITS总分与安慰剂相比均显著增加（分别为p = 0.005和p = 0.041）。在OLT结束时，仅他达拉非OaD组与安慰剂组相比改善显著（p = 0.035）。SEAR方面未观察到显著差异。
这些结果表明，长期服用他达拉非可改善nsRP术后患者的生活质量。随机接受他达拉非OaD治疗的老年患者尿失禁的改善可能有助于这一效果实现。
