Methadone versus Fentanyl in Patients with Radiation‐Induced Nociceptive Pain with Head and Neck Cancer: A Randomized Controlled Noninferiority Trial

Haumann, Johan; Kuijk, Sander M. J. van; Geurts, José W.; Hoebers, Frank; Kremer, Bernd; Joosten, Elbert A.J.; Everdingen, M.H.J. van den Beuken-van

doi:10.1111/papr.12609

Cited by 16 publications

(10 citation statements)

References 34 publications

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“…In a randomized controlled trial of 52 patients, Haumann et al demonstrated that methadone was superior to fentanyl for neuropathic pain due to HNC . A subsequent randomized controlled trial of 82 patients demonstrated the noninferiority of methadone to fentanyl specifically for patients with HNC experiencing radiation‐induced pain; the authors also found less need to escalate opioids with the use of methadone …”

Section: Discussionmentioning

confidence: 99%

A single‐institution, randomized, pilot study evaluating the efficacy of gabapentin and methadone for patients undergoing chemoradiation for head and neck squamous cell cancer

Hermann

Iovoli

Platek

et al. 2019

Cancer

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Background The objective of the current study was to compare the safety and efficacy between 2 analgesic regimens for patients with head and neck cancer (HNC) undergoing definitive chemoradiation (CRT). Methods The current study was a prospective, single‐institution, 2‐arm, randomized pilot study. Patients with American Joint Committee on Cancer seventh edition stage II to stage IV squamous cell carcinoma of the head and neck who were undergoing CRT were randomized to either arm 1, which entailed high‐dose gabapentin (2700 mg daily) with the institutional standard of care (hydrocodone and/or acetaminophen progressing to fentanyl as needed), or arm 2, which comprised low‐dose gabapentin (900 mg daily) with methadone. The primary endpoints were safety and toxicity. Secondary endpoints were pain, opioid requirement, and quality of life (QOL). Differences between the treatment arms at multiple time points were compared using a generalized linear mixed regression model with Sidak correction. Results A total of 60 patients (31 in arm 1 and 29 in arm 2) were enrolled from April 2015 to August 2017. There was no difference between the treatment arms with regard to adverse events or serious adverse events. Pain was not found to be different between the treatment arms. More patients in arm 1 did not require an opioid during treatment (42% vs 7%; P = .002). Patients in arm 2 experienced significantly better QOL outcomes across multiple domains, including overall health (P = .05), physical functioning (P = .04), role functioning (P = .01), and social functioning (P = .01). Conclusions High‐dose prophylactic gabapentin increased the percentage of patients who required no opioid during treatment. Methadone may improve QOL compared with a regimen of short‐acting opioids and fentanyl. However, pain was found to significantly worsen throughout treatment regardless of treatment arm, necessitating further studies to identify a more optimal regimen.

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Section: Discussionmentioning

confidence: 99%

A single‐institution, randomized, pilot study evaluating the efficacy of gabapentin and methadone for patients undergoing chemoradiation for head and neck squamous cell cancer

Hermann

Iovoli

Platek

et al. 2019

Cancer

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“…Haumann et al ran two RCTs to compare the use of methadone to fentanyl in both nociceptive and neuropathic pain domains in OM. Opioidnaïve patients reported significantly decreased average pain with the use of methadone at 3 weeks of treatment (29).…”

Section: Discussionmentioning

confidence: 98%

“…Methadone may be more effective for neuropathic pain and unlike other opiates, methadone has a long half-life, therefore providing prolonged pain relief (28). Methadone, when used in conjunction with gabapentin, improves pain control and several QoL/function metrics (20,29). While it is unclear whether high dose gabapentin adds additional benefit to methadone, we recommend the use of methadone for pain relief in patients not well controlled on high dose gabapentin and over-counter-analgesics.…”

Section: Discussionmentioning

confidence: 99%

Narrative review of the management of oral mucositis during chemoradiation for head and neck cancer

2021

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Oral mucositis (OM) can be a significant problem for patients undergoing radiation or chemoradiation for head and neck cancer. In modern clinical trials, grade 3-4 OM can be seen in over 40% of patients and can cause a significant impact on their quality of life (QOL). Despite this fact, strategies for the prevention and treatment of OM vary widely, with options including both lifestyle modifications and pharmaceuticals. Here we evaluate and summarize the current clinical interventions for the management of radiation-induced OM. The majority of the current evidence focuses on reducing OM related pain.These agents are detailed over multiple clinical trials including treatment modalities such as: GC4419, doxepin mouthwash, diphenhydramine-lidocaine-antacid (DLA) mouthwash, gabapentin, and methadone.While several strategies have been employed to prevent radiation-induced OM, there is currently no strong evidence for the routine use of these agents in the clinic. After summarization of these treatments, we offer practical guidance for the treatment of OM in the clinic. We recommend a multiagent approach of pharmacological and non-pharmacological treatments including oral rinses, home humidification, escalating doses of gabapentin, doxepin or DLA mouthwash, over the counter analgesics, and lastly methadone. These interventions are tailored to address the expected increase of severity of symptoms during the course of head and neck radiotherapy.

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“…A randomized controlled trial found that methadone gave better and faster relief of cancer pain with a neuropathic component, compared with fentanyl. 15,16 Reddy et al 17 found no significant difference in overall survival among cancer patients taking methadone compared with other opioids, whereas a systematic review suggested switching from morphine/oxycodone to methadone as 1 of 3 weak recommendations for the management of opioid-induced nausea and vomiting. 18 A comparative retrospective study showed that early switching to methadone may be useful for control of advanced cancer pain.…”

Section: Discussionmentioning

confidence: 99%

Assistance of a Palliative Care Certified Nurse in the Alleviation of Refractory Cancer Pain by Switching Opioids to Oral Methadone in a Japanese Outpatient Setting

Okayama

Matsuda

2021

J Hosp Palliat Nurs

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Although methadone has the potential to improve the management of cancer pain, it has some serious problems, such as respiratory depression and QT interval prolongation. Therefore, patients who are prescribed methadone must be educated, monitored, and supported by specialized medical staff, especially in the outpatient setting. We assessed the effectiveness of support from the palliative care certified nurse who used the checklists in opioid switching to oral methadone for patients with refractory pain. Through the multidisciplinary palliative care team at our hospital, 15 outpatients with cancer pain were prescribed oral methadone between April 2013 and December 2020, and 14 cases were successful in switching to methadone. After taking medication, the certified nurse called the patient's home daily for 3 to 5 days and confirmed that the patient had taken the methadone, the degree of pain, the number of rescue medications, and the appearance of side effects, such as respiratory depression. Careful management by a multidisciplinary team is essential for opioid switching to oral methadone administration for outpatients. Certified nurses may play an important role in maintaining safety and resolving the patients' and families' anxieties with respect to the prescription of methadone.

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Methadone versus Fentanyl in Patients with Radiation‐Induced Nociceptive Pain with Head and Neck Cancer: A Randomized Controlled Noninferiority Trial

Abstract: This is the first study to show noninferiority of methadone compared to fentanyl at 1 and 3 weeks in the treatment of radiation-induced nociceptive pain in patients with head and neck cancer.

Cited by 16 publications

References 34 publications

A single‐institution, randomized, pilot study evaluating the efficacy of gabapentin and methadone for patients undergoing chemoradiation for head and neck squamous cell cancer

A single‐institution, randomized, pilot study evaluating the efficacy of gabapentin and methadone for patients undergoing chemoradiation for head and neck squamous cell cancer

Narrative review of the management of oral mucositis during chemoradiation for head and neck cancer

Assistance of a Palliative Care Certified Nurse in the Alleviation of Refractory Cancer Pain by Switching Opioids to Oral Methadone in a Japanese Outpatient Setting

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