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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).

Author information

1
Polyclinique de l'ormeau, Tarbes, France. Electronic address: phpoulain@wanadoo.fr.
2
Assistance Publique-Hôpitaux de Paris, Paris, France.
3
Laboratoires Bouchara-Recordati, Puteaux, France.
4
Centre Oscar Lambret, Lille, France.
5
Centre Léon Bérard, Lyon, France.
6
CHU Nord, Amiens, France.
7
CHU L'Archet2, Nice, France.
8
CHI Alpes du Sud, Gap, France.
9
CH Lyon Sud, Pierre Bénite, France.

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, 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.

METHODS:

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.

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 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.

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.

KEYWORDS:

Cancer pain; methadone; opioid

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