Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
Division of Dental and Oral Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
Support Care Cancer. 2018 Sep;26(9):3241-3248. doi: 10.1007/s00520-018-4175-4. Epub 2018 Apr 7.
This phase II trial assessed the clinical benefit of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine (HMB/Arg/Gln) for preventing chemoradiotherapy (CRT)-induced oral mucositis (OM) in patients with head and neck cancer (HNC).
Patients with HNC receiving definitive or postoperative cisplatin-based CRT were enrolled. HMB/Arg/Gln was administered orally or per percutaneous endoscopic gastrostomy from the first day of CRT up to its completion. All patients received opioid-based pain control and oral care programs that we previously reported. The primary endpoint was the incidence of grade ≥ 3 OM (functional/symptomatic) according to the Common Terminology Criteria of Adverse Events version 3.0. Quality of life (EORTC QLQ-C30/PROMS) at baseline and upon radiotherapy at a dosage of 50 Gy were assessed.
Thirty-five patients with HNC were enrolled. Sixteen of them (45.7%) developed grade ≥ 3 OM (i.e., functional/symptomatic). The incidence of grade ≤ 1 OM (functional/symptomatic) was 51.5% at 2 weeks and 82.9% at 4 weeks after radiotherapy completion. Clinical examination revealed that 10 patients (28.6%) developed grade ≥ 3 OM. The incidence of grade ≤ 1 OM (clinical exam) was 80.0% at 2 weeks and 100% at 4 weeks after radiotherapy completion. Adverse events related to HMB/Arg/Gln were an increase in blood urea nitrogen and diarrhea, but were easily managed.
The addition of HMB/Arg/Gln to opioid-based pain control and oral care programs was feasible but still insufficient at reducing the incidence of CRT-induced severe OM. However, the benefit of HMB/Arg/Gln should not be neglected given the findings of clinical examinations and the rapid recovery from severe OM.
UMIN000016453.
本 II 期临床试验评估了β-羟基-β-甲基丁酸、精氨酸和谷氨酰胺（HMB/Arg/Gln）预防头颈部癌症（HNC）患者接受放化疗（CRT）诱导的口腔粘膜炎（OM）的临床获益。
招募接受根治性或术后含顺铂 CRT 的 HNC 患者。从 CRT 第一天开始至完成，HMB/Arg/Gln 口服或经皮内镜胃造口管给药。所有患者均接受我们之前报道的基于阿片类药物的疼痛控制和口腔护理方案。主要终点是根据不良事件通用术语标准 3.0 版（CTCAE v3.0）评估的≥3 级 OM（功能/症状）的发生率。在基线和放疗 50Gy 时评估生活质量（EORTC QLQ-C30/PROMS）。
共纳入 35 例 HNC 患者。其中 16 例（45.7%）发生≥3 级 OM（即功能/症状）。放疗后 2 周和 4 周时，≤1 级 OM（功能/症状）的发生率分别为 51.5%和 82.9%。临床检查显示 10 例（28.6%）患者发生≥3 级 OM。放疗后 2 周和 4 周时，≤1 级 OM（临床检查）的发生率分别为 80.0%和 100%。与 HMB/Arg/Gln 相关的不良反应是血尿素氮升高和腹泻，但易于管理。
在基于阿片类药物的疼痛控制和口腔护理方案的基础上添加 HMB/Arg/Gln 虽然可行，但仍不足以降低 CRT 诱导的严重 OM 的发生率。然而，鉴于临床检查结果和严重 OM 的快速恢复，不应忽视 HMB/Arg/Gln 的益处。
UMIN000016453。
