Randomized Phase III, Double-Blind, Placebo-Controlled Study of Prophylactic Gabapentin for the Reduction of Radiation Therapy-Induced Pain During the Treatment of Oropharyngeal Squamous Cell Carcinoma
Cook AE, Modh A, Ali H, Sheqwara J, Chang S, Ghanem T, Momin S, Wu V, Tam S, Han X, Fakhoury L, Movsas B, and Siddiqui F. Randomized Phase III, Double-Blind, Placebo-Controlled Study of Prophylactic Gabapentin for the Reduction of Radiation Therapy-Induced Pain During the Treatment of Oropharyngeal Squamous Cell Carcinoma. Int J Radiat Oncol Biol Phys 2021; 111(3):S61-S62.
Int J Radiat Oncol Biol Phys
Purpose/Objective(s): We sought to determine if prophylactic gabapentin usage in patients undergoing definitive concurrent chemoradiotherapy (chemoRT) for oropharyngeal cancer improves patient-reported quality of life (QOL) metrics, opioid analgesic requirements, and feeding tube (FT) placement.
Materials/Methods: This double-blind, randomized phase III study for patients with AJCC 7th 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. All patients received 70 Gy in 35 fx using IMRT. The primary endpoint was change in Patient-Reported Oral Mucositis Symptom (PROMS) scores from baseline over the study period. Opioid requirements (average over the entire study period and change from baseline, converted to daily morphine equivalents [DME]), FT placement, and other patient-reported QOL metrics (FACT-HN and PRO-CTCAE) were assessed. Questionnaires were administered at baseline, weekly during RT treatments, and at 6-week post-RT follow-up (f/u). Patients were considered compliant if they took at least 12 doses in any given week (self-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 P value less than 0.05 was considered statistically significant.
Results: There were 65 patients enrolled in the study and 7 withdrew consent, leaving 58 patients to be analyzed. Baseline characteristics were well-balanced, and only 1 patient was considered non-compliant. All patients completed RT as planned. No significant difference was found in PROMS scores between the two groups (P = 0.130). FT placement was significantly higher in the gabapentin vs placebo arm (64.3% vs 33.3%, P = 0.003). Of the FTs placed, 96% were Dobhoff tubes. There was no significant difference in terms of average opioid use (median 22.8 DME [IQR 12.8-36.5] vs 15.8 DME [IQR 8.3-32.4], P = 0.412) or change in opioid use (P = 0.818) for gabapentin vs placebo, respectively. For the FACT-HN questionnaire, the only significant difference noted was in the functional well-being index with the gabapentin arm having a significant decrease in scores from baseline to f/u (median -6 [IQR -10 to -1.5] vs -1 [IQR -5.75 to 5], P = 0.017) with lower scores suggesting poorer QOL. PRO-CTCAE scores increased significantly at f/u from baseline for gabapentin vs placebo (median 6 [IQR 3 to 11] vs 1 [IQR -2 to 6.5], P = 0.014) with higher scores suggesting worse QOL.
Conclusion: This study suggests that prophylactic gabapentin is not effective in improving pain related to mucositis during chemoRT in patients with oropharyngeal squamous cell carcinoma, and other strategies should be evaluated to minimize opioid usage in this patient population.