Cancer pain is common among patients with advanced disease, and strong opioids are the standard therapy for moderate to severe pain. Nonetheless, dose escalation of a single opioid does not always provide adequate analgesia. Low-dose methadone add-on therapy has attracted attention as a strategy to improve pain relief while maintaining tolerability. We retrospectively examined the efficacy and safety of low-dose methadone add-on therapy for uncontrolled cancer pain and explored clinical factors associated with treatment response. Adult patients with cancer who received low-dose methadone besides an ongoing strong opioid at our institution between May 2019 and March 2023 were reviewed. Safety was assessed in 39 patients. Efficacy was analyzed using an available case analysis, including only patients for whom numeric rating scale (NRS) data were available. Responders were defined as patients with a ≥30％ reduction in NRS from baseline by Day 14. The median NRS significantly decreased on Days 7 and 14 compared with Day 0 (6 vs 4; P < 0.01, 6 vs 3; P < 0.01). Within 14 days after methadone initiation, adverse events were primarily Grade 1 – 2 somnolence and constipation, and no treatment discontinuations due to adverse events occurred. The time from initiation of prior strong opioid to methadone add-on was significantly shorter in responders than in nonresponders, suggesting that earlier introduction of methadone may improve analgesic outcomes. These findings show that low-dose methadone add-on therapy is a useful and well-tolerated option for managing uncontrolled cancer pain in clinical practice.
