Efficacy of Prophylactic High-Dose Gabapentin and Venlafaxine among Patients Treated with Chemoradiation for Head and Neck Cancer: A Single-Institution Randomized Phase II Trial

Abstract

<h3>Purpose/Objective(s)</h3> More than 80% of patients treated with chemoradiation for head and neck cancer have been shown to experience oral mucositis, causing significant pain, dysphagia, and poor quality of life. Given emerging evidence of improved pain relief from adding venlafaxine to the prophylactic gabapentin regimen for painful diabetic neuropathy, we performed a single-institution, phase II trial randomizing prophylactic gabapentin with versus without venlafaxine among patients undergoing chemoradiation for head and neck cancer. <h3>Materials/Methods</h3> Our study was a prospective, single-institution, randomized trial involving patients with stage II-IV squamous cell carcinoma of the head and neck who underwent chemoradiation. Patients were randomized to either prophylactic gabapentin (3600 mg daily) with or without venlafaxine (150 mg daily). Methadone was used for breakthrough pain. Primary endpoint was differences in pain levels between two arms based on the EORTC QLQ-HN35 at the end of chemoradiation. Secondary endpoint was toxicity profiles, quality of life changes, opioid use, and feeding tube placement. Differences between two arms at multiple time points were evaluated using a generalized linear mixed regression model with Sidak correction. <h3>Results</h3> Between May 2018 and March 2021, a total of 62 patients were enrolled and 59 patients were evaluable for analysis (n=32 for the gabapentin alone arm, n=27 for the gabapentin + venlafaxine arm). Overall, more than 90% of patients tolerated the regimens well (93.8% [30/32] for the gabapentin alone arm and 92.6% [25/27] for the gabapentin + venlafaxine arm, p=0.86). No statistically significant differences between these two arms were noted with regard to adverse events, serious adverse events, head and neck pain, and quality of life measures. A total of 12 of 32 (37.5%) and 13 of 27 (48.1%) patients required opioids for additional pain control in the gabapentin alone and gabapentin + venlafaxine arms, respectively (p=0.44). Time to first opioid use (gabapentin alone arm: median 34 days, range 20-44; gabapentin + venlafaxine arm: median 33 days, range 25-42; p=0.76) was comparable between these two arms. By the end of treatments, 3 of 32 patients in the gabapentin alone arm had feeding tubes placed, while no patient in the gabapentin + venlafaxine arm underwent feeding tube placement (p=0.24). <h3>Conclusion</h3> To our knowledge, this is the first prospective trial to suggest that prophylactic gabapentin with 3600 mg daily is feasible and that the addition of venlafaxine did not result in improvements in pain control and quality of life among patients with head and neck cancer. Prophylactic gabapentin with 3600 mg daily has been adopted as our institutional standard regimen.