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

Abstract

<h3>Purpose/Objective(s)</h3> There have been no prior placebo-controlled prospective studies examining the role of gabapentin in HN cancer. We sought to determine if prophylactic gabapentin use in patients undergoing definitive concurrent chemoradiotherapy (chemoRT) for oropharyngeal cancer improves treatment-related pain, patient-reported QOL metrics, opioid analgesic requirements, and feeding tube (FT) placement as compared to placebo. <h3>Materials/Methods</h3> This double-blind, randomized phase III study for patients with AJCC 7^th ed stage III-IV oropharyngeal squamous cell carcinoma undergoing concurrent chemoRT randomly allocated patients to prophylactic gabapentin (600 mg TID) or placebo, stratified by smoking status. This dose was chosen to avoid dose adjustment in the setting of cisplatin-induced nephrotoxicity. All patients received 70 Gy in 35 fractions using IMRT concurrent with a platinum-based regimen. The primary endpoint was change in Patient-Reported Oral Mucositis Symptom (PROMS) scores from baseline to the 6-week post-RT follow-up time point (f/u). Other patient-reported QOL metrics (FACT-HN and PRO-CTCAE), opioid requirements (average over the entire study period and change from baseline, converted to daily morphine equivalents [DME]), and FT placement were assessed. Questionnaires were administered at baseline, weekly during RT treatments, and f/u. Patients were considered compliant if they took at least 12 doses in any given week (patient-reported). Repeated measures ANOVA was used to detect differences in PROMS scores and change in opioid use from baseline. Wilcoxon-rank sum tests were used to compare average opioid use, FACT-HN, and PRO-CTCAE scores. Chi-square test was used to compare FT placement. A <i>p</i>-value less than .05 was considered statistically significant. <h3>Results</h3> There were 65 patients enrolled and 7 withdrew consent, leaving 58 patients analyzed. Baseline characteristics were well-balanced, including stage, type of chemotherapy, and dosimetric parameters. Only 1 patient was non-compliant. All patients completed RT as planned. No significant difference was found in PROMS scores between the two groups at f/u (mean 29.1, SD 22.5, vs 20.1, SD 16.8, for gabapentin vs placebo, respectively, <i>p</i> = .11). The FACT-HN functional well-being index had a significant decrease in scores from baseline to f/u in the gabapentin arm (median -6, IQR -10.0 to -0.5, vs -1, IQR -5.5 to 3.0, <i>p</i> = .03, lower score=worse QOL). PRO-CTCAE scores increased significantly at f/u for gabapentin (median 6.5, IQR 3.5 to 11.8, vs 1, IQR -2.0 to 6.0, <i>p</i> = .01, higher scores worse). 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%, <i>p</i> < .01). <h3>Conclusion</h3> This study suggests that prophylactic gabapentin at 600 mg TID is not effective in improving treatment-related pain in a select group of patients.