OP-8 A feasibility randomized controlled trial comparing opioid dose escalation vs. methadone addition for refractory cancer pain
Notice bibliographique
Résumé
<h3>Background</h3> Cancer pain affects 38–85% of cancer patients, with higher incidence in advanced stages.<sup>1</sup> Poorly controlled cancer pain, often with neuropathic elements, presents a significant unmet medical need. Despite various opioid formulations, 47% of physicians report difficulties in managing opioid-refractory pain.<sup>2</sup> Methadone has shown superior efficacy to other opioids, such as morphine, especially for neuropathic pain poorly controlled by other opioids.<sup>3</sup> Currently, opioid escalation is the standard, but is often inadequate, and although the methadone add-on (AO) method has been reported to be safe and effective for refractory cancer pain, no randomized controlled trials (RCTs) have been conducted. <h3>Aims</h3> This study aims to explore the feasibility of conducting a double-blind RCT to assess the efficacy and safety of the methadone AO method for opioid escalation in patients with cancer pain. <h3>Methods</h3> This study is a single-facility, double-blind, parallel-arm RCT. A total of 22 patients will be enrolled between July 2024 and September 2025. Eligible participants are adults with unresectable advanced cancer experiencing refractory cancer pain on an appropriate dose of opioid analgesia (60–300 mg oral morphine equivalent daily dose, OMEDD) and a Karnofsky Performance Status (KPS) >50. Participants will be randomized (1:1) to the methadone AO arm or the standard treatment arm. Evaluations will be conducted at baseline (randomization), day 1, 8, and 15. In the methadone AO arm, patients will receive over-capsulated methadone 5 mg or 10 mg, and in the 5 mg group, placebo will be used to unify the twice-daily dosing of the study drug. In the standard treatment arm, patients will receive over-capsulated oxycodone 10 mg or 20 mg. The primary endpoint is the completion rate of the two-week study treatment, defined as 70% or more. Secondary endpoints include changes in BPI scores before and after the study treatment and adverse events. <h3>Discussion</h3> Several considerations influenced the study design. First, the methadone dosage required careful determination. Previous studies suggest equivalence ratios of OMEDD 30–90 = 4:1, 90–300 = 6:1, and over 300 = 8:1. For this study, we set the morphine-to-methadone ratio at 6:1, which is safer than the 3:1 and 5:1 reported in other studies but less conservative than NCCN recommended 10:1. Second, the primary endpoint was defined as achieving a study completion rate of at least 70%. Although no prospective clinical trials exist, a Canadian cohort study (N=146) reported a continuation rate of 78.1% at Day 15 with a mean methadone dose of 6 mg. This data and discussions within our study group, led us to set a 70% completion rate. Finally, we chose a 2-week study period based on previous research: Mercadante et al. (n=108) found stable methadone doses over 4 weeks, and Bruera et al. (n=103) reported over 20% pain relief by Day 8 with no dose change between Days 14 and 28. Thus, 2 weeks is sufficient for efficacy and safety assessment. Based on the results of our study, we plan to conduct a larger-scale RCT of the methadone to establish a treatment for refractory cancer pain. <h3>References</h3> Poulain P, Berleur MP, Lefki S,<i> et al</i>. Efficacy and safety of two methadone titration methods for the treatment of cancer-related pain: The EQUIMETH2 Trial (Methadone for Cancer-Related Pain). <i>J Pain Symptom Manage.</i> 2016 Nov;<b>52</b>(5):626–636.e1 Mercadante S, Porzio G, Ferrera P,<i> et al</i>. Sustained-release oral morphine versus transdermal fentanyl and oral methadone in cancer pain management. <i>Eur J Pain.</i> 2008 Nov;<b>12</b>(8):1040–6. Bruera E, Palmer JL, Bosnjak S, et al. Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study. <i>J Clin Oncol.</i> 2004 Jan 1;<b>22</b>(1):185–92.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».