New study aims to find an alternative therapy to tackle crippling bone pain suffered by cancer patients

Date: 12/05/2021

A generous clinical research grant donation from the Sambor family will allow Dr Merlina Sulistio and Associate Professor Natasha Michael to explore if methadone is a safe and effective alternative treatment option for patients suffering from debilitating cancer induced bone pain (CIBP).

Researchers Dr Sulistio and A/Prof Michael from the Supportive, Psychosocial and Palliative Care Research Department and Palliative and Supportive Care Service at Cabrini Health, will conduct the first prospective open-label study to examine if methadone is a safe and effective approach for managing CIBP. The researchers hope the study will identify patient characteristics that will allow clinicians to predict if a patient is more likely to respond to methadone treatment.

“If we show methadone is an effective alternative to other opioids, and we understand what it is about particular patients that respond well to methadone treatment, we can start to look at guidelines that will help clinicians make treatment decisions” A/Prof Michael said.

Dr Merlina Sulistio and Associate Professor Natasha Michael

Dr Merlina Sulistio (left) and Associate Professor Natasha Michael (right)

“If we can find ways to manage pain better and reduce ineffective treatment, we have achieved greatly for patients who suffer immensely from bone pain.”

A greater understanding of how debilitating cancer bone pain should be treated is needed

Pain management remains a challenge in the treatment of advanced cancer, with up to a third of patients not receiving appropriate medication to effectively control their pain intensity. Cancer pain commonly arises from metastatic disease (reemergence of the cancer in distant new locations), with bone being the most frequent site of metastasis. Pain occurs due to cancer induced bone destruction (osteolysis), which causes inflammatory and neuropathic pain through a combination of direct tumour sensory neuron activation, bone microfractures, and release of growth factors and cytokines. A third of patients with bone metastases suffer from debilitating CIBP, causing poor quality of life, psychological distress, depression and anxiety.

Current treatment for CIBP includes radiotherapy, radioisotopes, surgery, interventional procedures and pharmacological management. To date, opioids such as morphine remain the main pharmacological treatment for CIBP despite studies in animals suggesting a level of resistance to opioids in CIBP, and a lack of evidence to guide their use in the clinic.

Methadone is a potent synthetic opioid with a novel mechanism of action compared to other opioids. The Palliative and Supportive Care Service at Cabrini Health, along with other health centres, frequently use racemic methadone as an alternative opioid in patients with CIBP who are unresponsive to morphine or other opioids, or who exhibit opioid dose-limiting toxicity. Despite its use in treating CIBP however, many questions around its effectiveness as an alternative opioid and the characteristics of patients who are most likely to respond to it remain unanswered. The research team have already started to examine these questions and have recently published the first retrospective cohort study to review outcomes of methadone treatment for CIBP in a health institution.  The study showed that methadone treatment resulted in a 30 per cent reduction in pain in 70 per cent of patients. Patients also required a reduced daily dose of methadone and experienced less frequent breakthrough pain following treatment with methadone. These results show promising preliminary evidence that methadone for refractory CIBP might provide benefits, but this requires confirmation by further exploratory studies. Dr Sulistio said the new prospective open-label study would address many limitations they had in the first study because it was conducted retrospectively.

“We will be able to do things like make observations over a longer period, maintain consistency in how pain intensity is scored, and control for the impact of concurrent treatments,” she said.

“This first of its kind prospective study will properly establish the efficacy of methadone treatment versus other opioids, its tolerability, and safety to use. We are hopeful it will highlight a cohort of patients who are more likely to respond to methadone as this will significantly assist clinicians in treatment planning and management of patients with CIBP.”

This project is supported by a generous donation made by the Sambor family for advancements in clinical research. Donations allow us to do research that advance new treatment options and provide better care, ensuring there is a brighter health future for all those in need.