Coluzzi P H, Schwartzberg L, Conroy J D, Charapata S, Gay M, Busch M A, Chavez J, Ashley J, Lebo D, McCracken M, Portenoy R K
The Oncology Center at St. Joseph Medical Plaza, 1140 West LaVeta, Suite 450, Orange, CA 92868, USA.
Pain. 2001 Mar;91(1-2):123-30. doi: 10.1016/s0304-3959(00)00427-9.
Oral transmucosal fentanyl citrate (OTFC); Actiq) is a drug delivery formulation used for management of breakthrough cancer pain. Previous studies with open-label comparisons indicated OTFC was more effective than patients' usual opioid for breakthrough pain. The objective of this study was to compare OTFC and morphine sulfate immediate release (MSIR) for management of breakthrough pain in patients receiving a fixed scheduled opioid regimen. This double-blind, double-dummy, randomized, multiple crossover study was conducted at 19 US university- and community-based hospitals and clinics and comprised 134 adult ambulatory cancer patients. Patients were receiving a fixed scheduled opioid regimen equivalent to 60-1000 mg/day oral morphine or 50-300 microg/h transdermal fentanyl, were using a 'successful' MSIR dose (15-60 mg) as defined by entry criteria, and were experiencing 1-4 episodes of breakthrough pain per day. In open-label fashion, OTFC was titrated such that a single unit (200-1600 microg) provided adequate pain relief with acceptable side effects. Successfully titrated patients entered the double-blind phase of the study and received ten prenumbered sets of randomized capsules and oral transmucosal units. Five sets were the successful OTFC dose paired with placebo capsules, and five sets were placebo OTFC paired with capsules containing the successful MSIR dose. Patients took one set of study medication for each episode of target breakthrough pain. Pain intensity (PI), pain relief (PR) and global performance of medication (GP) scores were recorded. Pain intensity differences (PID) were calculated and 15-min PID was the primary efficacy variable. Adverse events were recorded. Sixty-nine percent of patients (93/134) found a successful dose of OTFC. OTFC yielded outcomes (PI, PID, and PR) at all time points that were significantly better than MSIR. GP also favored OTFC and more patients opted to continue with OTFC than MSIR following the study. Somnolence, nausea, constipation, and dizziness were the most common drug-associated side effects. In conclusion, OTFC was more effective than MSIR in treating breakthrough cancer pain.
口腔黏膜用枸橼酸芬太尼（OTFC，商品名：Actiq）是一种用于治疗癌症突破性疼痛的药物剂型。以往的开放标签对照研究表明，OTFC在治疗突破性疼痛方面比患者常用的阿片类药物更有效。本研究的目的是比较OTFC和硫酸吗啡速释片（MSIR）在接受固定剂量阿片类药物治疗方案的患者中治疗突破性疼痛的效果。这项双盲、双模拟、随机、多次交叉研究在美国19家大学和社区医院及诊所进行，纳入了134例成年门诊癌症患者。患者接受相当于口服吗啡60 - 1000mg/天或透皮芬太尼50 - 300μg/小时的固定剂量阿片类药物治疗方案，使用符合入选标准定义的“有效”MSIR剂量（15 - 60mg），且每天经历1 - 4次突破性疼痛发作。以开放标签方式滴定OTFC剂量，使单个单位（200 - 1600μg）能提供充分的疼痛缓解且副作用可接受。成功滴定剂量的患者进入研究的双盲阶段，接受十组预先编号的随机胶囊和口腔黏膜给药单位。五组是成功的OTFC剂量与安慰剂胶囊配对，另外五组是安慰剂OTFC与含有成功MSIR剂量的胶囊配对。患者针对每次目标突破性疼痛发作服用一组研究药物。记录疼痛强度（PI）、疼痛缓解（PR）和药物总体疗效（GP）评分。计算疼痛强度差值（PID），15分钟时的PID为主要疗效变量。记录不良事件。69%的患者（93/134）找到了有效的OTFC剂量。OTFC在所有时间点的疗效指标（PI、PID和PR）均显著优于MSIR。GP评分也更倾向于OTFC，研究结束后，选择继续使用OTFC的患者比选择MSIR的患者更多。嗜睡、恶心、便秘和头晕是最常见的与药物相关的副作用。总之，OTFC在治疗癌症突破性疼痛方面比MSIR更有效
