Journal Article

Efficacy and safety of combining low-dose methadone with ongoing opioid treatment for uncontrolled cancer pain: an open-label single-arm study

Akechi, Tatsuo, Kubota, Yosuke, Uchida, Megumi, Harada, Yoshihiko, Hasegawa, Takaaki, Furukawa, Yosuke, Yamakawa, Hideo, Okuyama, Toru, Iida, Moeko, Tasaki, Yoshihiko, Ito, Asako, Kikuchi, Shino, Suzuki, Nana

2025

Overview

Abstract Background Pharmacological options for refractory cancer pain are limited. This study aimed to investigate the efficacy and safety of the combined use of low-dose methadone and ongoing opioid treatment for uncontrolled cancer pain. Methods This was a prospective, open-label study. Participants were patients with uncontrolled cancer pain despite dose titration of opioids. Patients received low-dose methadone (starting dose of 5 or 10 mg/day) combined with another ongoing opioid therapy. The primary outcome was the proportion of responders (defined as ≥33% reduction in average pain intensity on the numerical rating scale [NRS]) on day 15. Pain intensity and adverse events according to the Patient-Reported Outcome Common Terminology Criteria for Adverse Events were evaluated at baseline, on days 8 and 15. Results Nineteen patients participated in this study, 11 (57.9%) of whom had neuropathic pain. The mean daily oral morphine equivalent dose before combination was 112.6 mg. The primary outcome occurred in 13 (68.4%) of patients (95% CI, 43.4 to 87.4). The mean average NRS was 5.9 at baseline, which decreased significantly to 4.2 and 3.3 on days 8 and 15 (P < .001), respectively. The worst pain intensity on NRS decreased significantly over time. Adverse effects, including nausea, vomiting, constipation, and somnolence, which were new or had worsened from baseline, were reported in 26.3%, 26.3%, 5.3%, and 26.3%, respectively. Delirium was observed in one patient. Conclusion Low-dose methadone with ongoing opioid treatment shows potential efficacy in the management of uncontrolled pain with acceptable adverse events. ClinicalTrials.gov identifier UMIN000038924

• Publisher: Oxford University Press
• Subject: Adult / Aged / Analgesics, Opioid - administration & dosage / Analgesics, Opioid - adverse effects / Analgesics, Opioid - therapeutic use / Cancer / Cancer pain / Cancer Pain - drug therapy / Cancer Pain - pathology / Care and treatment / Dosage and administration / Drug therapy / Drug therapy, Combination / Female / Humans / Male / Methadone - administration & dosage / Methadone - adverse effects / Methadone - therapeutic use / Methadone hydrochloride / Middle Aged / Morphine / Nausea / Neoplasms - complications / Oncology, Experimental / Pain / Palliative treatment / Prospective Studies / Testing / Treatment Outcome