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 the superiority of methadone over fentanyl in neuropathic pain, and we expect that this finding could influence the number of patients treated with methadone. Methods 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. Results 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. Conclusion 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.