Background:~Methadone is an opioid that has been used for over 80 years to treat various types of pain, including cancer pain. Its use as a co-analgesic and first-line treatment for cancer pain is becoming more widespread. Despite its increasing popularity, there remain some outstanding questions regarding its use in treating cancer pain, such as its efficacy compared to other opioids and its appropriateness as a first-line treatment.~Traditional classifications of cancer related chronic pain is classified as neuropathic and nociceptive (somatic or visceral). This classification is based on clinical descriptors as opposed to pathophysiologic mechanisms. The investigators propose a new mechanism, called 'adenocarcinopathic' pain (ACPP), which can be defined as pain caused by an adenocarcinoma that is in 'proximity' to or invading a nerve or nerve plexus. The suggested mechanism of ACPP is that the tumour excretes excess glutamate, which activates NMDA receptors on nearby sensory nerves, causing the pain sensation. As methadone is an NMDA antagonist (and mu receptor agonist), it becomes an interesting molecule for ACPP in comparison to other opioids (such as morphine) that are unable to suppress NMDA receptors.~Study Hypothesis:~Methadone will demonstrate superior efficacy to morphine for the treatment of ACPP, and physicians will demonstrate satisfactory confidence in its use.~Study Objectives:~Monitor safety and response to treatment~Evaluate the confidence of physicians~Study Design:~Participants will be randomized to receive either methadone or morphine. Patients will be observed for a period of 14 days, plus one physician follow-up after 28 days.~Sample Size & Study Population:~The investigators will aim to enrol n=40 patients total across all sites. Eligible outpatients are those for whom a strong opioid is being initiated or escalated for the treatment of ACPP.~Intervention:~For patients previously taking 0-30mg morphine equivalent daily dose (MEDD), starting dose is 0.5mg Q4H for methadone, 2.5mg for morphine. For those previously taking 31-60 mg MEDD, starting dose is 1.0mg Q4H for methadone, 5.0mg for morphine. Up to 4 breakthrough analgesia doses allowed per day. Dose escalations can be made at each patient encounter according to a standard dosing schedule.~Study Outcome Measures:~Using validated questionnaires, the patient's degree of pain control & relief, degree of satisfaction, global impression of change, and any side effects will be assessed. In addition, physicians will be asked to rate their confidence in treating each patient.~Expected Outcomes:~Positive results should provide justification to prolong the study to complete a phase III trial.
Methadone is an opioid that has been used for over 80 years to treat various types of pain, including cancer pain. Despite its increasing popularity as a co-analgesic and first-line treatment for cancer pain, there remain some outstanding questions regarding its use in treating cancer pain, such as its efficacy compared to other opioids and its appropriateness as a first-line treatment. The investigators will conduct a Vanguard Randomized Clinical Trial (RCT) to estimate the efficacy of methadone compared to morphine for the treatment of a newly defined type of cancer pain, which the investigators have termed 'adenocarcinopathic' pain (ACPP).