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.