Staph Nasal Decolonization to Improve Function and Feeding

Radiation induced oral mucositis (RIOM) is a significant toxicity associated with curative head and neck radiotherapy leading to burdensome pain, weight loss, treatment interruptions and high healthcare utilisation. With contemporary treatment grade 3 or higher (CTCAE) oral mucositis rates occur in ~40% of all patients despite standardised oral care and supportive measures. There is growing evidence to implicate Staphylococcus aureus as a contributor to mucosal injury and symptom severity in this setting.

Skin and nasal carriage of S. aureus is common in the general population. In oncology patients auto-inoculation to the pharynx from the nose during treatment is biologically plausible. Intranasal antibiotics such as mupirocin are well-established, targeted decolonisation agents with a favourable safety profile when used intermittently, however their role in preventing severe radiation induced mucositis remains unknown.

Given RIOM typically emerges during weeks 2-3 of treatment and peaks towards the final treatment a cyclical short-course of intranasal or topical antibiotic regimen may sustain decolonisation across the vulnerable window while limiting continuous antibiotic exposure and potential resistance selection. The Centres for Disease Control and Protection recommend intranasal mupirocin when implementing decolonisation or pathogen reduction strategies for high risk patients during high risk periods.

A recent single-centre phase 3 randomised trial of 176 nasopharynx patients demonstrated a 25% reduction in grade 3 or higher oral mucositis rates when treated with cyclical nasal mupirocin decolonisation. This evidence led us to our research question- is this result applicable in a more generalised head and neck cancer population? SNIFF is a pragmatically designed randomised, placebo-controlled trial to test whether cyclical intranasal antibiotic reduces patient reported pain outcomes (NRS scale 0-10 measured weekly) due to reduction in rates of severe mucositis in patients receiving curative-intent head and neck radiotherapy (oral cavity, oropharynx, locally- advanced larynx, hypopharynx). The trial will also evaluate its effects on analgesia adjusted pain scores, physician reported mucositis rates patient reported quality of life (QOL) and rates of feeding tubes or treatment interruptions.

Please note: This trial will be run in a single centre (LHSC, London, Ontario)- the medication used in the experimental arm is topical Mupirocin 2% ointment, as the nasal form is not marketed in Canada. As the medication is being used off-label, we have applied to Health Canada via a Clinical Trial Application, and received a No-objection letter on Jan 14th 2026 (Health Canada control number 304222).

Inclusion criteria

• Histologically confirmed mucosal squamous cell carcinoma of the head and neck, planned to receive a dose equivalent to 60 Gy in 30 fractions or higher, with or without concurrent systemic treatment. This can include hypofractionated regimens of 55 Gy in 20 fractions. Primary sites considered: oral cavity, oropharynx, larynx (excluding T1-T2N0 glottic cancers), hypopharynx. The radiotherapy treatment planned can be definitive or adjuvant.
• Age ≥18 years.
• ECOG performance status 0-2
• Informed consent provided.

Exclusion criteria

• Mupirocin allergy
• Skin or salivary gland malignancy
• Early stage glottic cancers (T1-2N0)