Randomized Phase III, Double Blind, Placebo-Controlled Study of Prophylactic Gabapentin for the Reduction of Oral Mucositis Pain During the Treatment of Oropharyngeal Squamous Cell Carcinoma

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International journal of radiation oncology, biology, physics


PURPOSE: To determine if prophylactic gabapentin usage in patients undergoing definitive concurrent chemoradiotherapy (chemoRT) for oropharyngeal cancer (OPC) improves treatment-related oral mucositis pain, opioid use, and feeding tube (FT) placement.

METHODS AND MATERIALS: This double-blind, randomized phase III study for patients with locally advanced OPC undergoing chemoRT randomly allocated patients to prophylactic gabapentin (600 mg thrice daily) or placebo. The primary endpoint was change in Patient-Reported Oral Mucositis Symptom (PROMS) scores over the entire treatment period (baseline to 6 weeks post-RT follow-up) with higher scores indicating worse outcomes. Opioid requirements, FT placement, and other patient-reported QOL metrics (Functional Assessment of Cancer Therapy-Head and Neck [FACT-HN] and Patient-Reported Outcomes of Common Terminology Criteria for Adverse Events [PRO-CTCAE]) were assessed. Lower scores suggested poorer quality of life (QOL) with the FACT-HN questionnaire, and higher scores suggested worse outcomes with the PRO-CTCAE questionnaire. Questionnaires were administered at baseline, weekly during RT, and at 6-week post-RT follow-up. Repeated measures analysis of variance were used to detect differences in PROMS scores and change in opioid use from baseline. Wilcoxon-rank sum tests were used to compare averages for the other secondary endpoints. A p-value less than .05 was considered statistically significant.

RESULTS: Treatment arms were well-balanced overall, including T and N staging and dosimetric variables. There were 58 patients analyzed. No significant difference was found in PROMS scores (mean 29.1, Standard Deviation [SD] 22.5, vs 20.1, SD 16.8, for gabapentin vs placebo, respectively, p = .11). The FACT-HN functional well-being index had a significant decrease in scores from baseline to follow-up in the gabapentin arm (median -6, interquartile range [IQR] -10.0 to -0.5, vs -1, IQR -5.5 to 3.0, p = .03). PRO-CTCAE scores increased significantly at follow-up for gabapentin (median 6.5, IQR 3.5 to 11.8, vs 1, IQR -2.0 to 6.0, p = .01). There was no significant difference in average or change in opioid use. FT placement was significantly higher in the gabapentin arm (62.1% vs 20.7%, p < .01).

CONCLUSIONS: This study suggests that prophylactic gabapentin is not effective in improving treatment-related oral mucositis symptoms in a select population of patients with OPC undergoing definitive chemoRT.

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ePub ahead of print