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J Pain Symptom Manage. 2016 Nov;52(5):626-636.e1. doi: 10.1016/j.jpainsymman.2016.05.022. Epub 2016 Sep 30.

Efficacy and Safety of Two Methadone Titration Methods for the Treatment of Cancer-Related Pain: The EQUIMETH2 Trial (Methadone for Cancer-Related Pain).

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Polyclinique de l'ormeau, Tarbes, France. Electronic address:
Assistance Publique-Hôpitaux de Paris, Paris, France.
Laboratoires Bouchara-Recordati, Puteaux, France.
Centre Oscar Lambret, Lille, France.
Centre Léon Bérard, Lyon, France.
CHU Nord, Amiens, France.
CHU L'Archet2, Nice, France.
CHI Alpes du Sud, Gap, France.
CH Lyon Sud, Pierre Bénite, France.



In the European Association for Palliative Care recommendations for cancer pain management, there was no consensus regarding the indications, titration, or monitoring of methadone.


This national, randomized, multicenter 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.


The primary end point 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 two consecutive days) and no overdose (Rudkin scale ≥3 and respiratory rate <8/minute). The patients were followed for two months after enrollment.


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 three 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.


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.


Cancer pain; methadone; opioid

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