Efficacy and safety of two methadone titration methods for the treatment of cancer-related pain: The EQUIMETH2 trial (methadone for cancer-related pain)

• Published in: Journal of pain and symptom management Vol. 52; no. 5; pp. 626 - 636.e1
• Main Authors: Poulain, Philippe, Berleur, Marie-Pierre, Lefki, Shimsi, Lefebvre, Danièle, Chvetzoff, Gisèle, Serra, Eric, Tremellat, Fibra, Derniaux, Alain, Filbet, Marilène
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2016; Elsevier Limited
• Subjects: Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Anesthesia & Perioperative Care; Breakthrough Pain; Cancer; Cancer pain; Cancer Pain - drug therapy; Clinical trials; Drug Overdose; Efficacy; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Medical treatment; Methadone; Methadone - administration & dosage; Methadone - adverse effects; Middle Aged; Multicenter studies; opioid; Opioids; Overdoses; Pain management; Pain Measurement; Pain Medicine; Palliative care; Patient safety; Retreatment; Safety; Treatment Outcome; Cancer pain; methadone; opioid
• ISSN: 0885-3924; 1873-6513
• DOI: 10.1016/j.jpainsymman.2016.05.022

Abstract Context In the European Association for Palliative Care recommendations for cancer pain management, there was no consensus regarding the indications, titration or monitoring of methadone. Objectives This national, randomized, multicentre trial aimed to compare two methadone titration methods (stop-and-go vs progressive) in patients with cancer-related pain who were inadequately relieved by or intolerant to level 3 opioids. Methods The primary endpoint was the rate of success/failure at Day 4, defined as pain relief (reduction of at least two points on the visual scale and a pain score <5 for 2 consecutive days) and no overdose (Rudkin scale ≥3 and respiratory rate <8/min). The patients were followed for 2 months after enrolment. Results The cancer-related pain characteristics of the 146 patients were as follows: 16% were nociceptive, 85% experienced breakthrough pain, and 84% had mixed types of pain. The reasons for switching to methadone were a lack of efficacy that was either isolated (56%) or associated with intolerance (38%). Adequate pain relief was obtained in 80% of the patients (median of 3 days in both groups [p = 0.12]) and lasted until D56. The rate of success/failure was approximately 40% at Day 4 in both groups, with overdoses in 13% of the patients throughout the study. The two methods were considered equally easy to perform by nearly 60% of the clinicians. Conclusion Methadone is an effective and sustainable second-line alternative opioid for the treatment of cancer-related pain. The methods of titration are comparable in terms of efficacy, safety and ease of use.