Background: 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. Methods: 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. Results: 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. Conclusions: EC-18 administered orally may be a safe and effective CRT-associated SOM intervention in patients with HNC.
背景：口腔黏膜炎（OM）是头颈癌（HNC）同步放化疗（CRT）中一种重要的毒性反应。本研究评估了先天免疫反应调节剂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。方法：本研究为一项两阶段、二期、随机、双盲、安慰剂对照、多中心试验。第一阶段为盲法平行组剂量探索安全性及耐受性研究，共纳入24名受试者，平均分为四组，分别接受EC-18（500毫克、1000毫克或2000毫克）或安慰剂治疗。第二阶段将受试者按1:1比例随机分配至安慰剂组或2000毫克EC-18组。自放疗首日至放疗结束日（LDRT）期间每日给药两次。患者每周接受两次评估。口腔黏膜炎评分采用世界卫生组织（WHO）标准进行集中评定。不良事件依据美国国家癌症研究所不良事件通用术语标准4.0版（NCI-CTCAE v4.0）进行报告。肿瘤反应随访报告至放疗结束后12个月。结果：在累积放疗剂量至少达到55戈瑞的患者中，超过80%在治疗前28天内依从研究给药方案，并持续使用研究药物超过4周。与安慰剂相比，EC-18有效缩短了严重口腔黏膜炎的持续时间，延迟了其发生时间，并降低了其发生率。EC-18治疗组患者的阿片类药物使用时间有所延迟。疗效与每周顺铂使用及人乳头瘤病毒（HPV）阳性状态相关。研究队列间不良事件发生率无显著差异。结论：口服EC-18可能是头颈癌患者中一种安全有效的同步放化疗相关严重口腔黏膜炎干预措施。
肿瘤(癌症)患者之家