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

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.