Methadone versus Fentanyl in Patients with Radiation-Induced Nociceptive Pain with Head and Neck Cancer: A Randomized Controlled Noninferiority Trial

Background Pain is still a burden for many patients with cancer. A recent trial showed superiority of methadone over fentanyl in neuropathic pain, and we expect that this could increase the amount of patients treated with methadone. Methods We performed a randomized controlled non-inferiority trial in patients with nociceptive pain. 82 strong-opioids naive patients with head-and-neck cancer with substantial pain (pain NRS≥4) due to radiation therapy were included. Forty-two patients were treated with methadone, and forty with fentanyl. Patients were evaluated at one, three, and five weeks. The primary outcomes were reduction in average pain and clinical success (50% pain decrease). We set the predefined non-inferiority margin at 1 on the NRS scale and 10% clinical success. Secondary outcomes were pain interference, global perceived effect (GPE), side effects, and opioid escalation index Results Non-inferiority was shown for decrease in NRS for maximum and mean pain scores at one and three weeks. Non-inferiority was shown for clinical success at one week only. The opioid escalation index was lower in the methadone group at three and five 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 three weeks only. GPE and side effects were not different. Conclusion This is the first study to show non-inferiority of methadone compared to fentanyl at one and three weeks in the treatment of radiation induced nociceptive pain in patients with head and neck cancer. This article is protected by copyright. All rights reserved.