Hashemi Masoud, Zali Alireza, Golmakani Ebrahim, Delshad Mohammad Hossein, Shadnoush Mahdi, Akbari Mohammad-Esmaeil
Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Functional Neurosurgery Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Daru. 2021 Jun;29(1):51-59. doi: 10.1007/s40199-020-00381-6. Epub 2021 Jan 21.
Breakthrough pain (BTP) is an important challenge in treatment and requires a rapid onset of action for pain control. BTP should be adequately controlled with a stable dose of a short-acting oral opioid. So far, no drug is available for the treatment of BTP in cancer patients in Iran, so we designed the first study in Iran to investigate the effect of sublingual fentanyl in relief of pain episodes in these patients.
The purpose of this study was to evaluate the efficacy and safety of sublingual fentanyl in the treatment of breakthrough pain in cancer patients.
This study was a randomized double-blind placebo-controlled clinical trial in cancer patients with breakthrough pain (at least 1-4 episodes of acute pain with moderate to severe pain daily) referred to the pain clinic of Akhtar and Masih Daneshvari hospitals in 2019. The study consisted of two stages: 100 patients were selected by simple, non-random sampling and entered the open-label titration phase. The primary efficacy endpoint was the sum of pain intensity difference over 30 min post-administration. Secondary efficacy endpoints included pain intensity difference (PID) and pain relief (PR) throughout the 60-min post-dose assessment period. In the double-blind study, patients were randomly divided into two groups of placebo (n=50) and intervention (sublingual fentanyl tablet) (n=50). For evaluation of efficacy, 10 episodes were treated in each group and the results were recorded by the patient. (Clinical trial registration: IRCT20131124015515N8).
A total of 100 patients entered the titration phase, primary efficacy of sublingual fentanyl was 3.5±0.6 and secondary efficacy of sublingual fentanyl (60 min, after treatment) was 0.3±0.6 which was statistically significant. In the titration phase, the treatment success rate was 100%. In the double-blind phase of the study, the pain intensity in multiple episodes showed a significant improvement at 15, 30, 45, and 60 min after drug administration (P=0.0001). The intensity of pain in each episode was significantly decreased compared to the next episode (P=0.0001). The mean frequency of pain episodes in the sublingual fentanyl group showed a significant decrease (P=0.0001). The most common adverse drug events in the titration phase were drowsiness (20%), dizziness (7%), and nausea 4%, and in the double-blind phase only drowsiness (12%). (Cancer Research Center, Shahid Beheshti University of Medical Sciences, Survey).
Sublingual fentanyl appears to be effective for patients with rapid-onset analgesia, has short-acting duration, is effective medication, safe, and well tolerated. It is a suitable choice in Iranian patients with chronic cancer-related pain controlled suffering from acute pain episodes related to cancer.
爆发性疼痛（BTP）是治疗中的一项重要挑战，需要药物迅速起效以控制疼痛。BTP应通过稳定剂量的短效口服阿片类药物得到充分控制。到目前为止，伊朗尚无药物可用于治疗癌症患者的BTP，因此我们在伊朗开展了第一项研究，以调查舌下含服芬太尼对这些患者疼痛发作的缓解效果。
本研究旨在评估舌下含服芬太尼治疗癌症患者爆发性疼痛的疗效和安全性。
本研究为一项随机双盲安慰剂对照临床试验，研究对象为2019年转诊至阿赫塔尔医院和马西赫·达内什瓦里医院疼痛门诊的患有爆发性疼痛（每天至少有1 - 4次中度至重度急性疼痛发作）的癌症患者。该研究包括两个阶段：通过简单非随机抽样选取100名患者，进入开放标签滴定阶段。主要疗效终点为给药后30分钟内疼痛强度差值之和。次要疗效终点包括给药后60分钟评估期内的疼痛强度差值（PID）和疼痛缓解情况（PR）。在双盲研究中，患者被随机分为安慰剂组（n = 50）和干预组（舌下含服芬太尼片）（n = 50）。为评估疗效，每组治疗10次发作，结果由患者记录。（临床试验注册号：IRCT20131124015515N8）
共有100名患者进入滴定阶段，舌下含服芬太尼的主要疗效为3.5±0.6，舌下含服芬太尼的次要疗效（治疗后60分钟）为0.3±0.6，具有统计学意义。在滴定阶段，治疗成功率为100%。在研究的双盲阶段，多次发作时的疼痛强度在给药后15、30、45和60分钟时均有显著改善（P = 0.0001）。与下一次发作相比，每次发作的疼痛强度均显著降低（P = 0.0001）。舌下含服芬太尼组疼痛发作的平均频率显著降低（P = 0.0001）。滴定阶段最常见的药物不良事件为嗜睡（20%）、头晕（7%）和恶心（4%），双盲阶段仅嗜睡（12%）。（设拉子医科大学癌症研究中心调查）
舌下含服芬太尼似乎对起效迅速的镇痛患者有效，作用持续时间短，是一种有效的药物，安全且耐受性良好。对于患有与癌症相关慢性疼痛且遭受与癌症相关急性疼痛发作的伊朗患者而言，它是一个合适的选择。
