Bacterial Decolonization With Mupirocin Ointment for Acute Radiation Oral Mucositis Prevention: A Phase 3 Randomized Clinical Trial

Abstract

Importance: Acute radiation oral mucositis (AROM) is a major dose-limiting toxic effect in patients with nasopharyngeal cancer undergoing radiotherapy. Reduction of severe (grade ≥3) AROM by bacterial decolonization (BD) could improve treatment tolerance and quality of life.

Objective: To evaluate the efficacy of BD with mupirocin nasal ointment in alleviating severe AROM compared with standard of care (SoC) by reducing Staphylococcus aureus colonization in nasal and oral mucosal during radiotherapy for nasopharyngeal cancer.

Design, setting, and participants: This was a single-center, open-label, phase 3 randomized clinical trial in China that enrolled patients with nasopharyngeal carcinoma (NPC) undergoing definitive chemoradiotherapy between July 2023 and February 2024. Data were analyzed from June 2024 to September 2024.

Interventions: The BD group received mupirocin nasal ointment twice daily for 3 days before radiotherapy for 5 consecutive days followed by a 1-week break, which was repeated throughout radiotherapy. Patients in the SoC group received routine nasal and oral care.

Main outcomes and measures: The primary outcome was the incidence of severe (grade ≥3) AROM. Oral mucositis assessments were performed by independent evaluators who were blinded to group assignments. Secondary end points included quality of life assessed using the Quality-of-Life Questionnaire-Head and Neck 43 [QLQ-H&N43]), and the colonization levels of S aureus in nasal and oral mucosa.

Results: A total of 176 patients (mean [SD] age, 52.1 [10.1] years; 42 female [23.9%] individuals) were randomly assigned to the BD intervention group (n = 88) or the SoC control group (n = 88). In the BD group, severe AROM occurred in 20 of 88 patients (22.7%) compared with 42 (47.7%) in the SoC group (relative risk, 0.48; 95% CI, 0.31-0.74; P < .001). Multivariable logistic analysis confirmed the effect of BD (odds ratio, 0.27, 95% CI, 0.13-0.54; P < .001) on severe AROM risk reduction. The QLQ-H&N43 assessment showed BD significantly reduced symptom severity compared to SoC during radiotherapy, with lower median (IQR) pain scores (25.0 [25.0-50.0] vs 50.0 [25.0-50.0]) and fewer swallowing difficulties (8.3 [8.3-33.3] vs 33.3 [8.3-33.3]). Colonization rates of S aureus at the end of radiotherapy were lower in the BD than in the SoC group: nasal, 9.4% (8 of 85) vs 22.9 % (19 of 83) and oral, 5.9% (5 of 85) vs 20.5% (17 of 83).

Conclusions and relevance: This phase 3 randomized clinical trial demonstrated that BD with mupirocin nasal ointment effectively reduced severe AROM, improved quality of life by alleviating oral pain and swallowing difficulties, and significantly reduced both nasal and oral S aureus colonization during radiotherapy. This approach offers a cost-effective strategy for AROM management, and although further studies are required to validate the findings, these results highlight the potential of microbial management to reduce radiation-related complications in patients with nasopharyngeal carcinoma.

Trial registration: ClinicalTrials.gov Identifier: NCT05893810.