Prophylactic Gabapentin Combined with Methadone Improves Overall Health in Patients Undergoing Chemoradiation for Head and Neck Cancer While Reducing Use of Opioids with High Abuse Potential: Early Results of a Prospective Randomized Trial

Abstract

Oral mucositis occurs in the majority of patients (pts) undergoing chemoradiation therapy (CRT) for head and neck cancer (HNC). The Oral Mucositis Daily Questionnaire (OMDQ) is a validated survey for HNC patient pain. Gabapentin (GABA) has been used concurrently with opioids to improve pain control in pts with HNC. Methadone (MTD) is a low abuse potential opioid that is used for neuropathic pain. This single center prospective randomized study was undertaken to compare analgesia regimens for pts undergoing CRT. Hypothesis: We hypothesized pts treated with GABA would have improved pain control and delay the onset of narcotic requirement, and the addition of MTD would provide improved pain control. Pts with Stage II-IV HNC who were treated with definitive CRT were randomized to one of two pain regimens: 1) High-dose GABA (900mg TID) with hydrocodone-acetaminophen followed by transdermal fentanyl as needed (HD-HAF) or 2) Low-dose GABA (300mg TID) with methadone (5-15mg BID) and oxycodone as needed (LD-MTD). Pts were stratified by bilateral or unilateral radiation. At baseline and weekly on-treatment visits, clinical data including narcotic use was recorded and OMDQ was administered. Average daily narcotic use was converted to oral morphine milligram equivalents. Two sided T and Fischer exact tests were performed. A total of 60 pts were randomized; at the time of analysis not all patients had completed their scheduled evaluations. Median dose to the primary was 70 Gy. There were no attributable grade 3 adverse events. Approximately half of HD-HAF and three quarters of LD-MTD required a narcotic during CRT. The time to first narcotic was approximately 4.5 weeks for both groups. LD-MTD had better Overall Health at week 7 vs. HD-HAF (p<0.05). This study demonstrates that both pain regimens are safe and well tolerated. Methadone is associated with better overall health at the end of treatment for pts undergoing CRT. Our next study will utilize high dose GABA and methadone. Implications for practice or research: Methadone, as a low abuse potential narcotic, combined with prophylactic GABA can improve overall health at the end of CRT for HNC. Further escalating GABA dose may optimize the therapeutic benefit of MTD and will be tested in a future study.