Effect of Lithium Mouthwash on Oral Mucositis and Taste Dysfunction in Head and Neck Radiotherapy: The Phase I/II Clinical Trial.

BACKGROUND: Oral mucositis (OM) and taste dysfunction (TD) are common oral complications of radiotherapy (RT) among head and neck cancer (HNC) patients, significantly impairing treatment outcomes and quality of life. PURPOSE: The purpose of this study is to evaluate the effectiveness and safety of a lithium-containing mouthwash in the management of OM, and explore its potential protection against TD. METHODS: This prospective single-institutional phase I/II trial enrolled patients with HNC undergoing definitive or postoperative adjuvant RT. Patients received a lithium-containing mouthwash or placebo thrice daily during RT. The phase I study evaluated any dose-limiting toxicity and determined the dose for phase II. The primary endpoint in phase II was the incidence of severe OM (SOM). Secondary endpoints included the time to onset and duration of SOM, taste alteration, the incidence of dry mouth, quality of life, and safety. RESULTS: A total of 175 patients were enrolled, with 15 in phase I and 160 in phase II. 0.15 mol/L of lithium-containing mouthwash as determined in phase I was used in phase II study. In the phase II, the incidence of SOM was significantly lower in the lithium group as compared with the placebo group (34.2% vs. 52.1%; P= .0304). The time to onset of SOM (median, NE vs. 35.0 days; P= .0262) was also improved in the lithium group. Additionally, lithium-containing mouthwash alleviated TD during RT. Adverse events (AEs) were similar between groups, and no severe AEs related to lithium were observed. CONCLUSION: Lithium-containing mouthwash yielded a significant reduction in the incidence and time to onset of SOM with a good safety profile, and also showed potential for ameliorating TD induced by irradiation.