Low-Dose Gabapentin in Combination with Methadone May Improve QOL in Patients with HNC

Administering low-dose prophylactic gabapentin (Gralise) in combination with methadone (Diskets) may improve quality of life (QOL) in patients with head and neck cancer (HNC), compared with a regimen of short-acting opioids and fentanyl, according to a study published in Cancer.

The data also suggested that a high dose of gabapentin increased the percentage of patients with HNC who required no opioid during treatment. However, pain was found to be significantly worse throughout treatment, regardless of treatment arm, indicating the necessity for further studies to identify a more optimal regimen.

“Given the body of work demonstrating the benefit of gabapentin for patients undergoing radiation for HNC, patients were likely deriving benefits from gabapentin in both treatment arms,” the authors wrote. 

In this cohort of 60 patients with stage II to stage IV squamous cell carcinoma of the head and neck who were undergoing chemoradiation (CRT), 31 patients were randomized to arm 1, on which they received 2,700 mg daily of gabapentin along with the institutional standard of care (hydrocodone and/or acetaminophen progressing to fentanyl as needed), and 29 patients were randomized to arm 2, on which they were given 900 mg daily of gabapentin with methadone. 

There were no differences observed between the treatment arms in regard to adverse events or serious adverse events, as well as pain and weight loss outcomes. More patients on arm 1 did not require an opioid during treatment (42% vs 7%; P = .002), though patients on 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). Patients who received the lower dose of gabapentin also experienced a significantly faster return of the global health scale to baseline after CRT (4 weeks for patients in arm 2 vs 4-6 months for patients in arm 1; P = .049). 

In the methadone arm, less insomnia and less fatigue reported may be attributed to the improved QOL. Fatigue is known to reduce QOL, often being associated with treatment discontinuation, though fatigue tended to be less with methadone (P = .06). Additionally, methadone has a relatively long duration of analgesia, allowing it to be dosed less frequently, potentially resulting in patients being able to sleep without interruption (sleeping P = .06). 

Of note, despite 42% of the patients on arm 1 requiring no opioids (zero MME), the patients on arm 2 treated with methadone had a 64% less total narcotic requirement (580 ± 409 MME vs 1,629 ± 1,849 MME; P = .11). Given this observation, “methadone compared with hydrocodone followed by fentanyl likely is even more effective than suggested by the current data,” the authors wrote. 

Researchers did however indicate potential concerns regarding the generalizability of the findings. Although it has not been widely considered addictive, gabapentin has been shown to have abuse potential. Moreover, though the researchers did not record cardiac toxicity using methadone in this study, high doses of methadone have previously been associated with fatal arrhythmias secondary to prolongation of the QTc interval. As a result, the researchers suggested that analgesic strategies should be distinguished for each individual patient, taking into consideration comorbidities and concurrent medications. 

According to the American Society of Clinical Oncology, HNCs account for about 4% of all cancers in the US. In 2019, it was estimated that 65,410 people would develop HNC, and an estimated 14,620 deaths would result from the disease.

References:

1. Hermann GM, Iovoli AJ, Platek AJ, et al. A Single-Institution, Randomized, Pilot Study Evaluating the Efficacy of Gabapentin and Methadone for Patients Undergoing Chemoradiation for Head and Neck Squamous Cell Cancer. Cancer. doi: 10.1002/cncr.32676.

2. Cancer.Net. Head and Neck Cancer: Statistics. ASCO website. Published January 2019. cancer.net/cancer-types/head-and-neck-cancer/statistics. Accessed January 21, 2020.