A phase II study of HMB/Arg/Gln against oral mucositis induced by chemoradiotherapy for patients with head and neck cancer
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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.
KeywordsHead and neck cancer Chemoradiotherapy Oral mucositis HMB/Arg/Gln Oral care
The authors thank Ms. Marina Kobayashi for data collection.
This study was supported by the Public Interest Incorporated Foundation - Shizuoka Industrial Foundation - Pharma Valley Center. The funders had no role regarding study design, data analysis, and the decision to publish or preparation of the manuscript.
Compliance with ethical standards
Conflict of interest
Tomoya Yokota serves in an advisory role for AstraZeneca, Merck Serono, Bayer, Ono Pharma CO., Ltd., and Bristol-Myers Squibb, and has received lecture fees from Merck Serono, Ono Pharma CO., Ltd., Eisai, Bayer, and Bristol-Myers Squibb.
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