Haumann Johan, van Kuijk Sander M J, Geurts José W, Hoebers Frank J P, Kremer Bernd, Joosten Elbert A, van den Beuken-van Everdingen Marieke H J
Department of Anesthesiology and Pain Management, Maastricht University Medical Centre, University Pain Centre Maastricht, Maastricht, The Netherlands.
Department of Anesthesiology and Pain Management, Onze Lieve Vrouwe, Amsterdam, The Netherlands.
Pain Pract. 2018 Mar;18(3):331-340. doi: 10.1111/papr.12609. Epub 2017 Aug 28.
Pain is still a burden for many patients with cancer. A recent trial showed the superiority of methadone over fentanyl in neuropathic pain, and we expect that this finding could influence the number of patients treated with methadone.
We performed a randomized controlled noninferiority trial in patients with nociceptive pain. Eighty-two strong-opioid-naïve patients with head and neck cancer with substantial pain (pain numeric rating scale [NRS] score ≥ 4) due to radiation therapy were included. Forty-two patients were treated with methadone, and 40 with fentanyl. Patients were evaluated at 1, 3, and 5 weeks. The primary outcomes were reduction in average pain and clinical success (50% pain decrease). We set the predefined noninferiority margin at 1 on the NRS and 10% clinical success. Secondary outcomes were pain interference, global perceived effect (GPE), side effects, and opioid escalation index.
Noninferiority was shown for decrease in NRS for maximum and mean pain scores at 1 and 3 weeks. Noninferiority was shown for clinical success at 1 week only. The opioid escalation index was lower in the methadone group at 3 and 5 weeks as compared to fentanyl (1.44 vs. 1.99, P = 0.004; and 1.50 vs. 2.32, P = 0.013). The pain interference in the methadone group was significantly decreased at 3 weeks only. GPE and side effects were not different.
This is the first study to show noninferiority of methadone compared to fentanyl at 1 and 3 weeks in the treatment of radiation-induced nociceptive pain in patients with head and neck cancer.
疼痛仍是许多癌症患者面临的负担。最近一项试验显示，在神经性疼痛方面美沙酮优于芬太尼，我们预计这一发现可能会影响接受美沙酮治疗的患者数量。
我们对伤害性疼痛患者进行了一项随机对照非劣效性试验。纳入82例因放射治疗导致严重疼痛（疼痛数字评定量表[NRS]评分≥4）的初治强阿片类药物的头颈癌患者。42例患者接受美沙酮治疗，40例接受芬太尼治疗。在第1、3和5周对患者进行评估。主要结局为平均疼痛减轻和临床成功（疼痛减轻50%）。我们将预先设定的非劣效性界值设定为NRS评分为1以及临床成功率为10%。次要结局为疼痛干扰、整体感知效应（GPE）、副作用和阿片类药物升级指数。
在第1周和第3周，美沙酮组在最大疼痛评分和平均疼痛评分的NRS降低方面显示出非劣效性。仅在第1周的临床成功方面显示出非劣效性。与芬太尼相比，美沙酮组在第3周和第5周的阿片类药物升级指数较低（分别为1.44对1.99，P = 0.004；以及1.50对2.32，P = 0.013）。仅在第3周，美沙酮组的疼痛干扰显著降低。GPE和副作用无差异。
这是第一项表明在治疗头颈癌患者放射性诱导的伤害性疼痛方面，美沙酮在第1周和第3周与芬太尼相比具有非劣效性的研究。
