Phase I/II trial of gabapentin plus intranasal ketamine for the prevention and treatment of pain in patients undergoing radiotherapy for head and neck cancer.
Year: 2024
Type: conference-abstract
Abstract: 12123 Background: Pain is ubiquitous in head and neck cancer (HNC) patients undergoing radiotherapy (RT) with up to 40% developing chronic pain. Gabapentin initiated concurrently with RT reduces pain intensity, opioid use, and dysphagia; however, gabapentin may not fully control pain, and dose escalation may be limited by toxicity. Novel non-opioid analgesic combinations administered concurrent with RT may address these limitations. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist. The NMDA receptor modulates mood and pain and is involved in central sensitization. Blocking the NMDA receptor may decrease the development and severity of neuropathic pain and decrease/prevent central sensitization. In combination with other analgesics, ketamine may enhance acute and chronic pain control at lower doses thus avoiding dose-limited toxicities. We report results from the dose-finding phase I study of gabapentin plus intranasal (NAS) ketamine in HNC patients undergoing RT; phase II is ongoing. Methods: Eligibility: locally advanced non-metastatic HNC planned for primary or adjuvant RT with or without concurrent chemotherapy. Primary objective of phase I was to determine the maximum tolerated dose (MTD) or maximum planned dose (MPD) for NAS ketamine combined with gabapentin (300mg TID). Planned dose levels (DL) were DL1: 10 mg TID, DL2: 20 mg TID, DL3: 30 mg TID and DL 4: 40 mg TID. A phase II expansion was planned at the MTD/MPD to confirm safety and feasibility. Results: Eleven patients were enrolled during phase I, which has been completed. No dose limiting toxicities (DLTs) were noted at DL1, DL2 or DL3. Two DLTs were reported at DL4: grade 2 dizziness and grade 2 sedation. The MTD was ketamine 30 mg NAS TID. Six patients are enrolled on the phase II trial at the MTD which is ongoing. Conclusions: The MTD of NAS ketamine was 30mg TID combined with gabapentin 300mg. The Phase II expansion is ongoing. Clinical trial information: NCT05156060 .
Source: Journal of Clinical Oncology
Institution: Vanderbilt University Medical Center
Language: English
Subfield: Anesthesiology and Pain Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4399672359