Gabapentin plus intranasal ketamine for the prevention and treatment of pain in patients undergoing radiotherapy for head and neck cancer: Phase II trial results.

Abstract

12135 Background: Prophylactic gabapentin decreases pain, opioid use, and weight loss in head and neck (HNC) patients treated with chemoradiotherapy. Nonetheless, significant symptom burden remains. Ketamine is an NMDA receptor antagonist which has neuromodulator and anti-inflammatory properties. We undertook a phase I/II study to explore safety, feasibility, and obtain preliminary efficacy data pertaining to the combination of ketamine and gabapentin in HNC patients undergoing radiation +/- chemotherapy. Results of the phase I study were previously reported. Herein we report preliminary results of the phase II portion of the study. Primary outcomes were toxicity and feasibility; secondary outcomes were symptom burden. Methods: Eligibility: locally advanced HNC patients planned for primary or adjuvant radiotherapy +/- chemotherapy. Treatment: Day 1: gabapentin 100 mg PO TID; Day 8: increase gabapentin to 300 mg PO TID; Day 15: continue gabapentin and start intranasal ketamine 30 mg TID. Dose modifications were allowed for both agents. Toxicity: assessed using CTCAE 5.0. Feasibility: data capture by pill counts and patient medication logs. Efficacy: patient reported outcomes measures completed at baseline, weekly during radiation and 1-, 2-, and 3-months post-radiation. Results: Patient characteristics: median age 60 yrs, 85% males, 67% p16-positive, 21 post-operative. Toxicity: Of 45 patients who completed treatment, 7 patients (16%) experienced a grade 2+ toxicity (5 were probably related to ketamine). Four patients required ketamine dose de-escalation due to dizziness. Six patients (13%) eventually discontinued ketamine due to toxicity. Feasibility: 41 (91%) patients missed <5% of gabapentin doses; 35 (78%) patients missed <5% of ketamine doses. Preliminary Efficacy: Eight patients (18%) required PEG placement. median score on the pain subscale of the Vanderbilt Head and Neck Symptom Survey 2.0 was highest at the end of treatment (4.3/10) and decreased rapidly (2.4/10 at 1 month and 1.7/10 at 2 months post-treatment). During treatment, 8 patients (18%) required no opioids, and 24 patients (55%) required immediate-release (IR) opioids only. The median of the maximum morphine milligram equivalent (MME) per day for IR opioids alone was 90 MME/day(range 10 – 180 MME/day). The median duration of IR prescription alone was 30 days (range 10 – 347 days). Twelve patients (27%) required addition of extended-release (ER) opioids with a median duration 35 days (range 28 - 220 days). Only 3 patients (7%) required ER opioids for >90 days. Conclusions: The combination of gabapentin and ketamine was safe and feasible. Preliminary data indicates the majority of patients experienced low to moderate levels of pain with minimal use of opioids. Larger, randomized studies are warranted to confirm the benefit of the combination of gabapentin and ketamine. Clinical trial information: NCT05156060 .