Departments of Radiation Oncology, Henry Ford Cancer Institute, Detroit, Michigan.
Department of Radiation Oncology, Mercy Health-Perrysburg Cancer Center, Perrysburg, Ohio.
Int J Radiat Oncol Biol Phys. 2022 Mar 15;112(4):926-937. doi: 10.1016/j.ijrobp.2021.11.012. Epub 2021 Nov 20.
The purpose of this paper is to determine whether prophylactic gabapentin usage in patients undergoing definitive concurrent chemotherapy and radiation therapy (chemoRT) for oropharyngeal cancer (OPC) improves treatment-related oral mucositis pain, opioid use, and feeding tube (FT) placement.
This double-blind, randomized phase 3 study for patients with locally advanced OPC undergoing chemoRT randomly allocated patients to prophylactic gabapentin (600 mg thrice daily) or placebo. The primary endpoint was change in Patient-Reported Oral Mucositis Symptom (PROMS) scores over the entire treatment period (baseline to 6 weeks post-radiation therapy [RT] follow-up) with higher scores indicating worse outcomes. Opioid requirements, FT placement, and other patient-reported quality of life (QOL) metrics (Functional Assessment of Cancer Therapy-Head and Neck [FACT-HN] and Patient-Reported Outcomes version of the National Cancer Institute Common Terminology Criteria for Adverse Events [PRO-CTCAE]) were assessed. Lower scores suggested poorer QOL with the FACT-HN questionnaire, and higher scores suggested worse outcomes with the PRO-CTCAE questionnaire. Questionnaires were administered at baseline, weekly during RT, and at 6 weeks post-RT follow-up. Repeated measures analysis of variance was used to detect differences in PROMS scores and change in opioid use from baseline. Wilcoxon rank sum tests were used to compare averages for the other secondary endpoints. A P value less than .05 was considered statistically significant.
Treatment arms were well balanced overall, including T and N staging and dosimetric variables. There were 58 patients analyzed. No significant difference was found in PROMS scores (mean 29.1, standard deviation [SD] 22.5 vs 20.1, SD 16.8 for gabapentin vs placebo, respectively, P = .11). The FACT-HN functional well-being index had a significant decrease in scores from baseline to follow-up in the gabapentin arm (median -6, interquartile range [IQR] -10.0 to -0.5 vs -1, IQR -5.5 to 3.0, P = .03). PRO-CTCAE scores increased significantly at follow-up for gabapentin (median 6.5, IQR 3.5-11.8 vs 1, IQR -2.0 to 6.0, P = .01). There was no significant difference in average or change in opioid use. FT placement was significantly higher in the gabapentin arm (62.1% vs 20.7%, P < .01).
This study suggests that prophylactic gabapentin is not effective in improving treatment-related oral mucositis symptoms in a select population of patients with OPC undergoing definitive chemoRT.
本文旨在确定在接受根治性同期放化疗（chemoRT）的口咽癌（OPC）患者中预防性使用加巴喷丁是否能改善与治疗相关的口腔粘膜炎疼痛、阿片类药物使用和置管（FT）。
这项针对接受 chemoRT 的局部晚期 OPC 患者的双盲、随机 3 期研究将患者随机分配至预防性加巴喷丁（600mg 每日三次）或安慰剂组。主要终点是整个治疗期间（从基线到放射治疗后 6 周随访）患者报告的口腔粘膜炎症状（PROMS）评分的变化，评分越高表明结果越差。评估了阿片类药物需求、FT 放置以及其他患者报告的生活质量（QOL）指标（癌症治疗功能评估-头颈部[FACT-HN]和患者报告的国家癌症研究所不良事件通用术语标准的结局版本[PRO-CTCAE]）。FACT-HN 问卷中得分较低表明 QOL 较差，而 PRO-CTCAE 问卷中得分较高表明结果较差。在基线、RT 期间每周和 RT 后 6 周随访时进行问卷调查。采用重复测量方差分析检测 PROMS 评分和从基线开始阿片类药物使用的变化差异。采用 Wilcoxon 秩和检验比较其他次要终点的平均值。P 值小于.05 被认为具有统计学意义。
治疗组总体上平衡良好，包括 T 和 N 分期和剂量学变量。共分析了 58 例患者。加巴喷丁组和安慰剂组的 PROMS 评分无显著差异（分别为 29.1，标准差[SD] 22.5 与 20.1，SD 16.8，P ＝.11）。加巴喷丁组 FACT-HN 功能健康指数的评分从基线到随访显著下降（中位数-6，四分位距[IQR] -10.0 至-0.5 与-1，IQR -5.5 至 3.0，P ＝.03）。PRO-CTCAE 评分在随访时显著增加（加巴喷丁组中位数 6.5，IQR 3.5-11.8 与 1，IQR -2.0 至 6.0，P ＝.01）。阿片类药物使用的平均值或变化无显著差异。加巴喷丁组 FT 放置比例显著较高（62.1% 与 20.7%，P <.01）。
本研究表明，在接受根治性同期放化疗的特定 OPC 患者人群中，预防性使用加巴喷丁并不能改善与治疗相关的口腔粘膜炎症状。
