Therapeutic Challenges in Cancer Pain Management: A Systematic Review of Methadone

Abstract

The proven therapeutic efficacy of methadone in cancer pain is hindered by a challenging pharmacokinetic-pharmacodynamic profile, considerable interpatient variation, and increasing concern about the complexities of dosing. The objective of this study was to assess the evidence for the use of methadone in cancer pain management. The authors conducted a systematic literature search for randomized controlled trials (RCTs) published post the 2007 Cochrane review of methadone in cancer pain. Trial quality was assessed using the Oxford Quality Scoring System and Cochrane Handbook for Systematic Reviews of Interventions. Of the 152 abstracts found, 4 were RCTs (272 participants). Two RCTs compared the efficacy and safety of methadone with placebo or active control and two investigated rotation to methadone from other opioids. The studies used different routes of administration, dosing, initiation, and titration of methadone and distinct pain scoring tools and did not address the issues raised by the Cochrane review. Methadone has an important role in the management of cancer pain, with many advantages including low cost, high oral bioavailability, rapid onset of action, once-daily dosing, and postulated benefits in difficult pain control scenarios. However, due to limited research in this area, methadone dosing remains a challenge, with vigilant dose initiation, adjustment, and monitoring required. There is a need for further studies using standardized methodology to evaluate the optimal dosing strategy of methadone, the effect on different types of pain, and the role of pharmacokinetics and pharmacogenomics in clinical outcomes.

Methadone versus Fentanyl in Patients with Radiation‐Induced Nociceptive Pain with Head and Neck Cancer: A Randomized Controlled Noninferiority Trial

“…4 When no difference between nociceptive and neuropathic pain was made, no difference in pain relief between morphine and methadone could be observed. A more recent systematic review, 23 based on 4 RCTs published after the 2007 Cochrane review, showed no difference in effectiveness between methadone compared to other strong opioids in 2 RCTs. 20,24 Two other RCTs used in this systematic review evaluated the effect of opioid rotation to methadone: in one study no conclusion on the efficacy of methadone in treatment of cancer pain could be presented due to the number of dropouts, 25 and the other reported a decrease in pain intensity switching from morphine to methadone and a patient preference for methadone.…”

Latin-American Guidelines for Cancer Pain Management

“…Some clinical studies suggest cardiovascular effects, such as prolongation of the QT interval or torsades de pointes. Given its long and variable half-life, potential interactions with several drugs, variability in conversion factors and the association with prolongation of the QT interval make methadone a drug with specific safety requirements [44].…”

Methadone in Pain Management: A Systematic Review

“…Three of these studies focus only on cancer-related pain and lack comprehensiveness, as they each include different RCTs. 20,38,47 Moreover, a recently published systematic review by D'Souza et al evaluates the use of methadone in postoperative pain control. 12 Several RCTs involving postprocedural pain are omitted from inclusion in the aforementioned review, however, and there is need for the evaluation of methadone's safety profile.…”