van Seventer R, Smit J M, Schipper R M, Wicks M A, Zuurmond W W A
Department of Anaesthesiology, Amphia Hospital, Breda, The Netherlands.
Curr Med Res Opin. 2003;19(6):457-69. doi: 10.1185/030079903125002045.
This randomised, multicentre, direct open comparative trial evaluated the efficacy, treatment convenience, tolerability and safety aspects of transdermal therapeutic system (TTS)-fentanyl and sustained-release oral morphine (SRM) in both opioid-naïve patients with moderate-to-severe cancer-related pain and in patients who had already been using opioids for mild-to-moderate pain. The two treatment groups were run in parallel. Special attention was paid to constipation, nausea/vomiting, drowsiness and respiratory depression.
The 131 enrolled patients started the 4-week treatment at low doses of opioid (25 microg/h TTS-fentanyl for 3 days or 30 mg SRM every 12 h) and were individually titrated. Tolerability, efficacy and safety were assessed throughout the study period. Frequency of constipation was the primary study variable and accordingly the study was powered for this. Both patients and investigators made a global treatment evaluation.
TTS-fentanyl and SRM were shown to be equally effective. Pain control and sleep quality improved with both treatments. None of the patients developed respiratory depression. Statistically significantly more patients in the SRM treatment group discontinued the trial prematurely (59% vs 27%; p < 0.001), particularly due to adverse events (36% vs 4%; p < 0.001). Fewer patients in the TTS-fentanyl than in the SRM treatment group reported constipation during the trial. This finding was statistically significant after 1 week of treatment (27% vs 57%; p = 0.003). The favourable tolerability profile of TTS-fentanyl was also reflected in both the patient and the investigator global evaluation of the treatment. Patient assessment favoured TTS-fentanyl treatment in terms of a significantly lower rate of troublesome side-effects ('quite a bit' to 'very much' troublesome side-effects in 14% vs 36% of patients; p = 0.003) and less interruption of daily activities (absence of any interruption of daily activities in 88% vs 63% of patients; p = 0.012). Investigators scored TTS-fentanyl as significantly better with respect to 'side-effects' (p = 0.039) and 'overall impression' (p = 0.013). Sub-analyses of opioid-naïve users gave similar results.
These data indicate that TTS-fentanyl, when used as an opioid of first choice in the treatment of cancer-related pain, is as effective as, but better tolerated than, SRM, including in opioid-naïve patients.
本随机、多中心、直接开放对比试验评估了透皮治疗系统（TTS）-芬太尼和缓释口服吗啡（SRM）在初用阿片类药物的中重度癌症相关疼痛患者以及已使用阿片类药物治疗轻至中度疼痛患者中的疗效、治疗便利性、耐受性和安全性。两个治疗组平行进行。特别关注便秘、恶心/呕吐、嗜睡和呼吸抑制情况。
131名入组患者以低剂量阿片类药物开始为期4周的治疗（TTS-芬太尼25微克/小时，持续3天，或SRM每12小时30毫克），并进行个体化滴定。在整个研究期间评估耐受性、疗效和安全性。便秘发生率是主要研究变量，研究也以此为依据进行了功效分析。患者和研究者均进行了整体治疗评估。
TTS-芬太尼和SRM显示出同等疗效。两种治疗方法均改善了疼痛控制和睡眠质量。没有患者出现呼吸抑制。SRM治疗组中统计学上显著更多的患者提前终止试验（59%对27%；p<0.001），尤其是由于不良事件（36%对4%；p<0.001）。在试验期间，TTS-芬太尼组报告便秘的患者少于SRM治疗组。治疗1周后这一发现具有统计学意义（27%对57%；p = 0.003）。TTS-芬太尼良好的耐受性也反映在患者和研究者对治疗的整体评估中。患者评估显示，就麻烦的副作用发生率显著较低而言（14%的患者有“相当多”到“非常多”麻烦的副作用，而SRM组为36%；p = 0.003）以及日常活动受干扰较少（88%的患者日常活动未受任何干扰，而SRM组为63%；p = 0.012），TTS-芬太尼治疗更具优势。研究者在“副作用”（p = 0.039）和“总体印象”（p = 0.013）方面给TTS-芬太尼的评分显著更高。对初用阿片类药物患者的亚组分析得出了类似结果。
这些数据表明，TTS-芬太尼作为治疗癌症相关疼痛的首选阿片类药物，与SRM疗效相当，但耐受性更好，包括在初用阿片类药物的患者中。
