口腔黏膜枸橼酸芬太尼：用于治疗癌症患者爆发性疼痛的随机、双盲、安慰剂对照试验。

Oral transmucosal fentanyl citrate: randomized, double-blinded, placebo-controlled trial for treatment of breakthrough pain in cancer patients.

作者信息

Farrar J T, Cleary J, Rauck R, Busch M, Nordbrock E

机构信息

University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

出版信息

J Natl Cancer Inst. 1998 Apr 15;90(8):611-6. doi: 10.1093/jnci/90.8.611.

DOI:10.1093/jnci/90.8.611

PMID:9554444

Abstract

BACKGROUND

Patients with cancer frequently experience episodes of acute pain, i.e., breakthrough pain, superimposed on their chronic pain. Breakthrough pain is usually treated with short-acting oral opioids, most of which provide some relief after 15-20 minutes, with peak effects after 30-45 minutes. Oral transmucosal fentanyl citrate (OTFC), a unique formulation of the opioid fentanyl, has been shown to provide meaningful pain relief within 5 minutes in patients following surgery. We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of OTFC for cancer-related breakthrough pain.

METHODS

Patients who were 18 years of age or older, receiving the equivalent of at least 60 mg oral morphine or at least 50 microg transdermal fentanyl per day for chronic cancer-related pain, and experiencing at least one episode of breakthrough pain per day were studied. After titration to an effective OTFC dose, subjects were given 10 randomly ordered treatment units (seven OTFC units and three placebo units) in the form of identical lozenges. If acceptable pain relief was not achieved within 30 minutes, subjects were instructed to take their previous breakthrough pain medication (i.e., rescue medication). Pain intensity, pain relief, and use of rescue medication were evaluated at 15-minute intervals over a 60-minute period.

RESULTS

Eighty-nine of 92 patients who received the randomized treatment were assessable (i.e., treated with at least one unit of OTFC and one unit of placebo). OTFC produced significantly larger changes in pain intensity and better pain relief than placebo at all time points (two-sided P<.0001). Episodes treated with placebo required the use of rescue medication more often than episodes treated with OTFC (34% versus 15%; relative risk = 2.27; 95% confidence interval = 1.51-3.26; two-sided P<.0001).

CONCLUSIONS

OTFC appears effective in the treatment of cancer-related breakthrough pain.

摘要

背景

癌症患者经常经历急性疼痛发作，即爆发性疼痛，叠加在其慢性疼痛之上。爆发性疼痛通常用短效口服阿片类药物治疗，其中大多数在15 - 20分钟后提供一定程度的缓解，30 - 45分钟后达到峰值效果。口服枸橼酸芬太尼（OTFC），一种独特的阿片类药物芬太尼制剂，已被证明在术后患者中5分钟内即可提供有效的疼痛缓解。我们进行了一项关于OTFC治疗癌症相关爆发性疼痛的多中心、随机、双盲、安慰剂对照试验。

方法

研究对象为年龄在18岁及以上、因慢性癌症相关疼痛每天接受相当于至少60毫克口服吗啡或至少50微克透皮芬太尼治疗且每天至少经历一次爆发性疼痛发作的患者。在滴定至有效的OTFC剂量后，受试者以相同含片的形式接受10个随机排序的治疗单位（7个OTFC单位和3个安慰剂单位）。如果在30分钟内未实现可接受的疼痛缓解，则指示受试者服用其先前的爆发性疼痛药物（即解救药物）。在60分钟内每隔15分钟评估疼痛强度、疼痛缓解情况以及解救药物的使用情况。

结果

92例接受随机治疗的患者中有89例可评估（即接受至少一个OTFC单位和一个安慰剂单位治疗）。在所有时间点，OTFC在疼痛强度方面产生的变化显著大于安慰剂，且疼痛缓解效果更好（双侧P <.0001）。与OTFC治疗的发作相比，安慰剂治疗的发作更常需要使用解救药物（34%对vs 15%；相对风险 = 2.27；95%置信区间 = 1.51 - 3.26；双侧P <.0001）。