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

Abstract

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.

Opioid therapy vs. multimodal analgesia in head and neck Cancer (OPTIMAL-HN): study protocol for a randomized clinical trial

“…Conversely, the pilot study conducted by Hermann et al randomized 60 HNC patients undergoing CRT for stage II-IV disease to either high-dose Gabapentin (2700 mg daily), Hydrocodone and/or Acetaminophen, progressing to Fentanyl as needed, or to low-dose Gabapentin (900 mg daily) with methadone. High-dose prophylactic Gabapentin appeared to reduce opioid requirements, but pain scores worsened throughout treatment irrespective of the analgesic regimen used [38]. No analgesic regimen has yet proven to effectively alleviate RIM pain during RT treatment.…”

“…Patients with HNC who are undergoing definitive RT with or without chemotherapy suffer significantly from RIM pain [2,3]. Two prospective studies, although with a limited sample size and mixed results, have assessed the safety and efficacy of different analgesic regimens for RIM pain [38,39]. In a pilot study, Kataoka et al randomized 22 stage III or IV patients receiving CRT to Acetaminophen and opioids alone or to Acetaminophen, opioids, and Gabapentin (900 mg daily).…”

Risk of Chronic Opioid Use After Radiation for Head and Neck Cancer: A Systematic Review and Meta-Analysis

“…Prophylactic gabapentin has been shown to reduce opioid requirements in patients with HNC receiving CRT. 18 This suggests that RIM pain likely requires a multimodal analgesic approach to address its nociceptive and neuropathic components for optimal pain relief.…”

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

“…Despite these overarching reviews, practical guidance on either the particular agent(s) to deploy or when to deploy them during the course of mucositis remains elusive (14,17). Furthermore, several additional treatments for OM during chemoradiation for head and neck cancer, including GC4419 (18), doxepin mouthwash (19), diphenhydraminelidocaine-antacid (DLA) mouthwash (19), gabapentin (20), and methadone (20), have been published since the MASCC/ ISOO review.…”