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Design and Participants: This open-label, observational study in 19 pain and palliative care centers evaluated efficacy and tolerability of low-dose methadone combined with another opioid in patients with moderate to severe cancer-related pain despite first-line opioid use (Numeric Rating Scale [NRS] ≥5/10 or Verbal Rating Scale [VRS] ≥3/5). All patients with cancer receiving care from the participating palliative care and pain teams were consecutively screened. Pain intensity, patients’ global impression of change (PGIC), and adverse effects were assessed day (D) 7 and D14. The main outcome was the proportion of responders. Analysis (intention to treat) used Friedman’s nonparametric ANOVA with Dunn’s post-hoc test.
Results: Patients (N=92) received a methadone daily dose of 3 mg (range=3-6) at baseline, 9 mg (4-10) D7, and 10 mg (6-15) D14. The NRS pain ratings decreased from 7 (6-8) at baseline to 5 (3-6) on D7 (P<.0001) and 4 (3-6) on D14 (P<.0001). Similarly, the VRS pain ratings decreased from 3 (3-3) at baseline to 2 (2-3) on D7 (P=.0026) and 2 (1-3) on D14 (P<.001). PGIC score was 1 (0-2) at D7 (P<.0001) and 1 (0.5-2) at D14 (P<.0001). In all, 53% and 50% were considered responders at baseline and D7, respectively. Of those responders, 74% were high responders at baseline and 59% were high responders at D7. No adverse events related to the risk of QT prolongation, overdose, or drug interactions were reported.
Commentary: Nearly half of patients with cancer will endure moderate or severe pain despite opioid treatment, and this study adds to the literature regarding the benefits of methadone use for refractory cancer pain. Study strengths include its prospective nature, multicenter design, and pragmatic approach. However, the noncontrolled observation design is a weaknesses. One major limitation is that the study cohorts’ baseline opioids were immediate release, as needed formulations (78% morphine or oxycodone, for example), so it is unclear if the improved pain ratings were related to the unique adjuvant effects of low-dose methadone or simply indicative of the patients’ need for the addition of a long-acting opioid (methadone or otherwise) in the setting of high opioid requirements (mean oral morphine equivalent daily dosing of 424 mg).
Bottom Line: Low-dose methadone added to immediate release, as-needed opioid regimens was safe and effective in improving moderate to severe refractory cancer pain.
Reviewer: Jason K. Bowman, MD, Baylor College of Medicine, Ben Taub Hospital, and Baylor St. Luke’s Medical Center, Houston, TX
References:
- Schuster M, Bayer O, Heid F, Laufenberg-Feldmann R. Opioid rotation in cancer pain treatment. Dtsch Arzteblatt Int. 2018;115(9):135-142. doi:10.3238/arztebl.2018.0135.
- Treillet E, Laurent S, Hadjiat Y. Practical management of opioid rotation and equianalgesia. J Pain Res. 2018;11:2587-2601. doi:10.3238/arztebl.2018.0135.
Source: Treillet E, Perceau-Chambard E, Economos G, et al. Low‑dose methadone added to another opioid for cancer pain: a multicentre prospective study. Support Care Cancer. 2024;32(11):716. doi:10.1007/s00520-024-08835-2.
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