Henson Christina, Clayburgh Daniel, Lee Arielle, Wong Deborah, Kudrimoti Mahesh, Lee Steve, Kalman Noah, Rao Krishna, Sohn Ki Young, Crawford Jeffrey, Villa Alessandro, Sonis Stephen
The Department of Radiation Oncology, Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA.
The Department of Otolaryngology, Portland VA Medical Center, Portland, OR 97239, USA.
Cancers (Basel). 2025 May 14;17(10):1663. doi: 10.3390/cancers17101663.
Oral mucositis (OM) remains a significant toxicity of concomitant chemoradiation (CRT) for head and neck cancer (HNC). This trial assessed the safety and efficacy of EC-18, an innate immune response mitigator, in attenuating severe OM (SOM) in HNC patients being treated with CRT.
This was a two-stage, Phase 2, randomized, double-blind, placebo-controlled, multi-institutional trial. Stage 1 consisted of a blinded parallel group dose-finding safety and tolerability study of 24 subjects in four equally sized groups of EC-18 (500 mg, 1000 mg, or 2000 mg or placebo). Stage 2 randomized subjects (1:1) to receive placebo or 2000 mg of EC-18. Twice-daily dosing was carried out from the first to the last day of radiation (LDRT). Patients were assessed twice weekly. OM scores were assigned centrally using WHO criteria. Adverse events were reported using NCI-CTCAE v4.0 criteria. Tumor response was reported up to 12 months following the LDRT.
Among patients who received a cumulative radiation dose of at least 55 Gy, at least 80% were compliant with the study's drug dosing during the first 28 days of treatment and continued to use the study drug for more than 4 weeks. EC-18 effectively reduced the duration, onset, and incidence of SOM compared to placebo. Opioid use was delayed in EC-18-treated patients. Efficacy was associated with weekly cisplatin use and HPV positivity. No significant differences in AEs were observed between study cohorts.
EC-18 administered orally may be a safe and effective CRT-associated SOM intervention in patients with HNC.
口腔黏膜炎（OM）仍然是头颈部癌（HNC）同步放化疗（CRT）的一种严重毒性反应。本试验评估了一种先天性免疫反应调节剂EC-18在减轻接受CRT治疗的HNC患者严重口腔黏膜炎（SOM）方面的安全性和有效性。
这是一项两阶段的2期随机双盲安慰剂对照多机构试验。第1阶段是一项盲法平行组剂量探索性安全性和耐受性研究，24名受试者分为四个等规模组，分别接受EC-18（500毫克、1000毫克或2000毫克）或安慰剂。第2阶段将受试者按1:1随机分组，接受安慰剂或2000毫克EC-18。从放疗第一天至最后一天（LDRT）每天给药两次。患者每周评估两次。使用世界卫生组织标准集中评定口腔黏膜炎评分。不良事件按照美国国立癌症研究所不良事件通用术语标准第4.0版（NCI-CTCAE v4.0）报告。放疗后长达12个月报告肿瘤反应情况。
在累积放疗剂量至少为55 Gy的患者中，至少80%的患者在治疗的前28天内遵守了研究的药物给药方案，并继续使用研究药物超过4周。与安慰剂相比，EC-18有效缩短了SOM的持续时间，延迟了其发作并降低了其发生率。接受EC-18治疗的患者使用阿片类药物的时间推迟。疗效与每周使用顺铂和人乳头瘤病毒（HPV）阳性有关。研究队列之间未观察到不良事件有显著差异。
口服EC-18可能是一种安全有效的CRT相关SOM干预措施，适用于HNC患者。
