Ernesto Zecca, Cinzia Brunelli, Fabio Centurioni, Andrea Manzoni, Alessandra Pigni, and Augusto Caraceni, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; and Cinzia Brunelli, Norwegian University of Science and Technology, Trondheim, Norway.
J Clin Oncol. 2017 Mar;35(7):759-765. doi: 10.1200/JCO.2016.69.9504. Epub 2017 Jan 23.
Purpose Fentanyl sublingual tablets (FST) are a potentially useful alternative to parenteral opioids such as subcutaneous morphine (SCM) to treat severe cancer pain episodes. No direct comparison between FST and SCM is available. The aim of this study was to test noninferiority of FST versus SCM during the first 30 min postadministration. Methods Patients receiving stable opioid therapy and experiencing a severe pain episode were randomly assigned to either 100 µg FST or 5 mg SCM in a double-blind, double-dummy trial. Average pain intensity (PI) assessed on a 0 to 10 numerical rating scale at 10, 20, and 30 min postadministration was the main end point. Analysis of covariance, adjusted by baseline PI, was the main analysis. The noninferiority margin (NIm) for the between-group difference was set at -0.6, that is, equal to one third of the minimum clinically important PI difference of two points. Results A total of 114 patients were randomly assigned to either FST (n = 58) or SCM (n = 56). One patient (in the FST group) withdrew consent before drug administration and was excluded from analysis. Baseline mean PIs were 7.5 in both groups; mean average PIs assessed at 10, 20, and 30 min postadministration were 5.0 and 4.5 for FST and SCM, respectively, with the 95% CI of the between-group difference including the NIm (-0.49; 95% CI, -1.10 to 0.09). Patients taking FST received a second drug dose after 30 min more frequently than did patients taking SCM (51% v 37%, respectively; risk difference, -13%; 95% CI, -30% to 3%). Both treatments were well tolerated, with average follow-up adverse event scores below the response of "A Little." Ninety-three percent of patients preferred the sublingual administration. Conclusion This trial did not show noninferiority of FST versus SCM within the chosen NIm. Both treatments were safe, and patients preferred the sublingual route of administration. FST provides analgesia with modest to moderate increased risk of lower efficacy compared with SCM.
芬太尼舌下片（FST）是一种潜在有用的替代药物，可替代皮下吗啡（SCM）等肠外阿片类药物，用于治疗严重的癌症疼痛发作。目前尚无 FST 与 SCM 之间的直接比较。本研究旨在检验 FST 与 SCM 在给药后 30 分钟内的非劣效性。
接受稳定阿片类药物治疗并经历严重疼痛发作的患者按双盲、双模拟设计随机分为 FST 组（100µg）或 SCM 组（5mg）。给药后 10、20 和 30 分钟时采用 0-10 数字评分量表评估平均疼痛强度（PI），为主要终点。采用协方差分析（按基线 PI 调整）进行主要分析。组间差异的非劣效性边界（NIm）设定为-0.6，即等于两点最小临床重要 PI 差异的三分之一。
共 114 例患者被随机分为 FST 组（n=58）或 SCM 组（n=56）。1 例患者（FST 组）在给药前撤回同意并被排除在分析之外。两组患者的基线平均 PI 均为 7.5；给药后 10、20 和 30 分钟时，FST 和 SCM 的平均平均 PI 分别为 5.0 和 4.5，组间差异的 95%CI 包含 NIm（-0.49；95%CI，-1.10 至 0.09）。给药 30 分钟后，接受 FST 治疗的患者比接受 SCM 治疗的患者更频繁地接受第二剂药物（分别为 51%和 37%；风险差异，-13%；95%CI，-30%至 3%）。两种治疗方法均耐受良好，平均不良事件评分低于“轻微”反应。93%的患者更喜欢舌下给药。
本试验未显示 FST 与 SCM 在所选 NIm 内的非劣效性。两种治疗方法均安全，患者更喜欢舌下给药途径。与 SCM 相比，FST 提供的镇痛效果适度至中度增加，疗效降低的风险增加。
