Methadone versus other opioids for refractory malignant bone pain: a pilot randomised controlled study

Abstract

Purpose: Refractory cancer-induced bone pain (CIBP) affects a patient's functional capacity and quality of life, but there is limited evidence to guide opioid choice. We assessed the feasibility, tolerability and possible efficacy of methadone rotation (MR) compared to other opioid rotations (OOR) in this cohort.

Methods: Adults with CIBP and worst pain intensity ≥ 4/10 and/or opioid toxicity graded ≥ 2 on the Common Terminology Criteria for Adverse Events were randomised 1:1 to methadone or another opioid rotation. Standardised assessment tools were used at pre-defined study time points up to 14 days.

Results: Of 51 eligible participants, 38 (74.5%) consented, and 29 (76.3%, MR: 14, OOR: 15) completed the fourteen days follow-up post-opioid rotation. Both groups displayed significant reduction in average (MR: d = - 1.2, p = 0.003, OOR: d = - 0.8, p = 0.015) and worst pain (MR: d = - 0.9, p = 0.042, OOR: d = - 0.6, p = 0.048) and total pain interference score (MR: d = - 1.1, p = 0.042, OOR: d = - 0.7, p = 0.007). Oral morphine equivalent daily dose was reduced significantly in MR compared to the OOR group (d = - 0.8, p = 0.05). The incidence of opioid-related adverse events following MR was unchanged but lower in the OOR group (d = 0.9, 95% CI 0.1,1.7, p = 0.022). There were no within-group or between-group differences in satisfaction with analgesia at the end of the study.

Conclusion: This pilot study demonstrated that MR and OOR in patients with refractory CIBP are feasible, safe and acceptable to patients. Appropriately powered multi-centre randomised controlled studies are needed to confirm the efficacy of MR and OOR in this cohort.

Trial registration: ACTRN12621000141842 registered 11 February 2021.

Keywords: Bone pain; Methadone; Opioid; Pain control; Refractory pain.

Fig. 1

Study procedure. AKPS, Australia-modified Karnofsky Performance Scale; BPI, Brief Pain inventory; CTCAE, Common Terminology Criteria for Adverse Events; DN4, Douleur Neuropathique 4; ECG, electrocardiogram; EuroQOL, quality of life standardised measure; HADS, hospital anxiety and depression scale; NRS, numerical rating scale; OEI, opioid escalation index; OMEDD, oral morphine equivalent daily dose for long-acting opioid analgesia; PICF, patient information and consent form

Fig. 2

CONSORT (Consolidated Standards of Reporting Trials) participant flow diagram. MR, methadone rotation; OOR, other opioid rotation; QTc, corrected QT interval. ^aNine rotated from oxycodone, six from fentanyl, three rotated from morphine and two from hydromorphone. ^bEight rotated from fentanyl to hydromorphone, six rotated from morphine to hydromorphone, three rotated from oxycodone to hydromorphone and one rotated from hydromorphone to oxycodone/naloxone. ^cWithdrawn from study

Fig. 3

Changes in pain intensity over time. MR, methadone rotation; NRS, numerical rating score; OOR, other opioid rotation