1-40 Rules Are Made to be Broken: Continuous Methadone for Intractable Cancer Pain

Rules Are Made to be Broken: Continuous Methadone for Intractable Cancer Pain

Catherine Habashy1, Catherine Habashy1, Doralina Anghelescu1, Sara Federico1

1) United States

Title: Rules Are Made to be Broken: Continuous Methadone for Intractable Cancer Pain

Background and aims: Management of severe cancer-related pain at the end of life often requires significant escalation of opioids, which commonly results in opioid-related side effects or tolerance. Methadone confers additional benefits over other opioids by limiting the development of opioid tolerance via antagonism at the NMDA receptor. However, its use has been hindered by its complex pharmacokinetic properties that result in highly variable analgesic response and potential toxicity. Little data exist on its safety and efficacy as a continuous infusion for management of refractory cancer pain.

Methods: This case report highlights the safety and efficacy of continuous methadone for intractable cancer-related pain at the end of life.

Results: We present a case of a 16 year-old boy with progressive, widely metastatic Ewing’s sarcoma. He began to experience severe bony pain despite a regimen of methadone 40 mg PO TID, hydromorphone PCA 50 mg/hr (boost 15 mg q10 min), and adjunctive therapy with gabapentin, dexamethasone and zoledronate. He was transitioned to continuous IV methadone 3 mg/h, which was titrated as an outpatient. After several weeks, he was readmitted for end of life care. Methadone was titrated further to 15 mg/hr without QTc prolongation (412 msec) or other signs of systemic toxicity. Ketamine 0.5 mg/kg/hr was added and hydromorphone was changed to fentanyl PCA 300 mcg/hr (boost 180 mcg q 5 min). He died peacefully with no signs of pain or distress.

Conclusions: Methadone is a synthetic opioid with dual activity as a mu opioid agonist and NMDA antagonist. Its pharmacokinetic properties are highly variable and limited data exist on its administration as a continuous infusion. This case provides support for its acceptability and utility as an approach to treating refractory cancer pain at the end of life.