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Patients with head and neck cancer undergoing radiation therapy are less likely to require opioids or a feeding tube if they received a higher dose of prophylactic gabapentin before their treatment, findings from a team of radiation oncologists at Roswell Park Comprehensive Cancer Center show. Their discovery, published in May in JAMA Network Open, suggests that a prophylactic, or preventative, gabapentin dose of 3600 mg daily can delay or eliminate the need for opioids to manage the pain associated with radiation-induced oral mucositis in patients with head and neck cancer.

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Nearly all patients who receive chemoradiation therapy to the head and neck area require opioids to manage oral mucositis, a painful side effect of radiation therapy for cancer.

“The use of opioids to control pain from oral mucositis is common among patients with head and neck cancer who are receiving chemoradiation therapy,” says Anurag Singh, MD, a radiation oncologist who serves as Director of Radiation Research at Roswell Park and is senior author of the new paper. “This pain builds during the weeks of therapy and can be severe enough to cause patients to stop treatment, which significantly worsens survival. This pain can also make it difficult to swallow, which can lead to severe weight loss, dehydration and kidney damage, necessitating feeding-tube placement.”

Gabapentin, a drug originally developed to prevent or minimize seizures, is also used to minimize side effects of chemoradiation. Hypothesizing that a higher dose of gabapentin would be more effective in reducing the need for a feeding tube or long-term opioids, and aiming to find an ideal dose of gabapentin, the Roswell Park team conducted a secondary analysis of two clinical trials enrolling patients who were receiving chemoradiation therapy for nonmetastatic squamous cell carcinoma of the head and neck.

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In two clinical trials, 92 patients received three different daily doses of prophylactic oral gabapentin: 900 mg, 2700 mg or 3600 mg. Most patients tolerated gabapentin well, but those who received the highest dose of gabapentin were significantly less likely to require opioids during radiation therapy — 93.1% of patients receiving 900 mg gabapentin required opioids to manage oral mucositis pain compared to only 37.5% of patients in the 3600 mg cohort.

“Nearly two-thirds of patients who received higher doses of gabapentin did not need opioids to manage pain at any point during their treatment,” says Sung Jun Ma, MD, Resident in the Department of Radiation Medicine and first author of the paper. “Patients who needed opioids for pain management took them later during the course of treatment when higher dose of prophylactic gabapentin was used, and fewer than 10% of patients who took high doses of gabapentin needed a feeding tube.”

The Roswell Park team is the first to report prospective data suggesting that higher doses of gabapentin were well tolerated and resulted in delayed time to first opioid use for pain control. Dr. Singh and colleagues have adopted the higher 3600 mg daily dose as standard of care in radiation therapy for head and neck cancer and continue to monitor the effects of this higher dose of gabapentin on overall quality of life among their patients.

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“This is a proven and safe strategy for not only controlling our patients’ pain but supporting optimal clinical outcomes and quality of life,” says Dr. Singh. “We are excited to share these findings with our radiation medicine colleagues internationally, and we encourage others to incorporate this practice into their care programs.”

This research was supported by National Cancer Institute grant P30CA016056, Roswell Park’s Cancer Center Support Grant from the NCI.