Patient prognosis was the cornerstone of a consensus statement on strategies for managing cancer pain in people with advanced disease and opioid use disorder (OUD).
Based on qualitative data from experts, gathered via an online modified Delphi process, the following recommendations were developed:
- For a patient with OUD taking buprenorphine-naloxone: Continue buprenorphine-naloxone with thrice-daily dosing.
- For a patient with a prognosis of weeks to months: Continue buprenorphine-naloxone and add a full-agonist opioid.
- For a patient with a prognosis of months to years: “[U]ncertain appropriateness” of continued buprenorphine-naloxone and full-agonist opioid add-on.
- For a patient with OUD taking methadone dispensed at a methadone clinic: Dose methadone outside the context of a methadone clinic three times per day.
- For a patient with a prognosis of weeks to months and on-treatment at a methadone clinic: Continue methadone daily and add another full-agonist opioid.
- For a patient with a prognosis of months to years: “[U]ncertain appropriateness” of continued methadone daily and full-agonist opioid add-on.
“Expert panels are conducted when no empirical evidence (e.g., randomized clinical trials) exists to answer a particular clinical question,” explained Jessica S. Merlin, MD, PhD, of the University of Pittsburgh, and co-authors in JAMA Network Open. “Delphi results are considered expert consensus-level evidence and may be used to generate clinical guidance.”
While the 120 experts who participated in the panels were fairly homogenous—median age 40-49, 94% White, 62% female, 96% with MD or DO degrees—the “variety of opinions among the experts in palliative care and addiction was striking,” noted Natalie Moryl, MD, and Vivek Tim Malhotra, MD, MPH, both of Memorial Sloan Kettering Cancer Center in New York City, in an invited commentary accompanying the study. They cited the example of palliative care providers green lighting the delivery of methadone to patients with cancer and OUD, but doing so outside “a structured methadone maintenance program” that monitors patients “in a way not done in the oncology setting,” which presents a whole separate challenge.
Other research supports that assertion from Moryl and Malhotra. In a 2021 Frontiers in Pain Research review, Jo Ann LeQuang, of Nema Research in Naples, Florida, and co-authors acknowledged that “[i]nitiating buprenorphine or methadone in a hospitalized cancer patient with OUD may facilitate patient management and prevent withdrawal symptoms, with the potential benefit that the patient may achieve recovery,” but also cautioned that management of these “patients out of the hospital setting is vastly different, and patients with substance use disorders [SUDs] have a high rate of leaving a hospital against medical advice.”
A 2020 review of case studies in Cureus, Ebubechukwu Ezeh, MBBS, of Marshall University in Huntington, West Virginia, and colleagues stressed that methadone “has been shown to be effective in managing OUD. It is also known that chronic opioid therapy may have the paradoxical effect of increased sensitivity to pain, a phenomenon called opioid-induced hyperalgesia (OIH). This presents a conundrum when a patient such as ours, on MAT [medication-assisted treatment] presents with acute pain and OIH.”
And, in a 2021 Journal of the Advanced Practitioner in Oncology case review, Gretchen A. McNally, PhD, and Ashley Sica, MSN, both of The Ohio State University James Cancer Hospital in Columbus, asserted that “[m]ost oncology clinicians are not prepared to confront the opioid epidemic or other SUDs.” In their case study, the patient with nodular sclerosis Hodgkin lymphoma and OUD was being treated at an outpatient methadone clinic but was found to be abusing alcohol and heroin when she was hospitalized for a possible cancer treatment-related infection.
“The emergency response team was called twice during her hospitalization. Early one morning, she was found unconscious; the Code Blue team was alerted and she recovered rather quickly. Security searched the hospital room and found a full syringe of an unknown substance. Following this episode and for her safety, the room door was left open, she was not allowed visitors, and a staff member was present for the remainder of the hospital stay. Due to Ms. Doe’s history of IV drug use, she was not prescribed opioids at discharge,” they wrote.
And in a 2021 Journal of Pain and Symptom Management study of “compassion inequities” and OUD in hospitalized patients with cancer, Sarah A. Singh, MD, of West Virginia University in Morgantown, and co-authors reported that “[o]ur results suggest that patients with OUD receive lower quality inpatient management of cancer-related pain. Provider education and early involvement of pain specialists are crucial in delivering equitable and compassionate end-of-life care for patients with OUD.”
So the building blocks for institutional and national guidelines are desperately needed and the current authors “demonstrated the urgent need for more data to inform the experts. In addition to palliative care and addiction experts, oncologists, interventional pain, mental health, and nursing professionals need to join at the table to discuss best practices in supporting and treating vulnerable patients with cancer pain and OUD,” according to Moryl and Malhotra.
Using the online ExpertLens, Merlin and co-authors conducted a three-round modified Delphi process from August to October 2020 with two cases: patient with advanced cancer, pain, and OUD treated with buprenorphine-naloxone or methadone. Merlin’s group offered more details on the Delphi process they used in a 2021 BMJ Open article.
Participating experts came from the fields of palliative care, addiction, or both, and recruited by email from palliative care and addiction-focused professional groups, from lists generated based on previous studies, and snowball sampling. The data were analyzed from November 2020 to July 2021.
The authors acknowledged that the [a]ppropriate expert selection is always a threat to Delphi study results,” and that the participant list did not include advanced practitioners, “who represent a substantial amount of the care provided to patients with advanced cancer in the U.S.” Other study limitations included that the results may not be generalizable to patients with advanced disease treated in oncology or primary care settings where palliative care services are not readily available.
In round one, participants rated management strategies, while they discussed results in round two, and gave final responses in round three. The authors reported that 70% of the participants took part in all three rounds.
Merlin and co-authors addressed some of the uncertainty regarding the recommendations, pointing out that the “choice between buprenorphine-naloxone and methadone in individuals with OUD, advanced cancer, and pain is complex. Although there is some evidence as to the efficacy of buprenorphine-naloxone and methadone for cancer pain” —per 2016 American Cancer Society/American Society of Clinical Oncology guidelines— “little is known about their comparative effectiveness with regard to pain or addiction outcomes in this patient population.”
Additionally, “methadone prescribing outside these programs is legal for pain, it is illegal for OUD; the implications for treating pain in individuals with OUD are uncertain,” and in the current study, “experts noted that attending methadone clinics may be burdensome and, for a seriously ill patient, even inappropriate.”
Not surprisingly, in-person methadone clinic visits took a hit during the pandemic. A 2020 STAT news article reported long lines outside clinics, despite federal regulations for daily visits being relaxed to minimize the spread of SARS-CoV-2.
The situation was dire enough that methadone clinic staff lodged complaints with the National Alliance for Medicated Assisted Recovery (NAMA), according to Zachary Talbott, NAMA president. “They’re calling because they’re worried about the patients, and they’re concerned that there is no social distancing,” he told STAT. “They’re also worried about themselves, because they have no personal protective equipment.”
Finally, Merlin’s group also stressed that cancer care specialists who treat this patient population are up against some legal issues, such as methadone licensure and waivers to prescribe buprenorphine-naloxone, and that costs associated with providing this type of care was not addressed in the current study.
An expert panel sanctioned continuing medication for opioid use disorder (OUD)—buprenorphine-naloxone or methadone—and to dose methadone outside the context of a methadone clinic thrice daily in patients with advanced cancer.
The appropriateness of adding full agonist opioids to either buprenorphine-naloxone or methadone is prognosis-dependent in this patient population.
Shalmali Pal, Contributing Writer, BreakingMED™
Merlin reported support from Cambia Health Foundation/University of Pittsburgh. Co-authors reported relationships with, and/or support from, ExpertLens, UptoDate, the NIH, Patient-Centered Outcomes Research Institute, The John A. Hartford Foundation, California Healthcare Foundation, Centene Foundation, Boye Foundation, West Health, and Aurora Health.
Moryl and Malhotra reported no relationships relevant to the contents of this paper to disclose.
Cat ID: 118
Topic ID: 78,118,730,118,935,192,144,397,922,925