KEY POINTS
- This single-centre randomized pilot trial enrolled 35 patients with head and neck cancer receiving radiotherapy to a prescribed dose >50 Gy, without concurrent chemotherapy. Patients entered the study after developing WHO grade 1-2 oral mucositis, usually approximately two weeks after starting radiotherapy.
- Patients were randomized to standard supportive care alone (n=17) or standard care plus 0.15% benzydamine hydrochloride spray, 4-8 sprays 4-6 times daily for 6 weeks (n=18).
- Oral mucositis progressed significantly more slowly with benzydamine. The longitudinal group-by-time interaction had an OR of 0.267 (95% CI 0.157-0.457, p<0.001) and substantially improved model fit compared with the model without interaction.
- Group separation became evident by week 3. At week 6, median mucositis grade was 2 with benzydamine versus 3 with standard care (p=0.0002).
- The largest clinical difference was severe mucositis: WHO grade ≥3 at week 6 occurred in 2/18 patients (11.1%) receiving benzydamine versus 12/17 (70.6%) with standard care, an absolute difference of 59.5 percentage points (p<0.001). Logistic regression yielded OR 0.052 (95% CI 0.006-0.268).
- Six patients were lost to follow-up after week 3, three in each arm. A complete-case sensitivity analysis in the 29 patients completing all six weeks remained concordant, with a group-by-time OR of 0.192 (95% CI 0.098-0.378, p<0.001).
- Most treated patients received at least 80% of prescribed benzydamine doses, and no benzydamine-related adverse events or treatment discontinuations were reported. Major limitations are the very small sample, open-label assessment, lack of placebo and retrospective trial registration.
CLINICAL TAKEAWAY
The magnitude of the reduction in severe mucositis is large enough to justify a definitive trial, particularly because the intervention is inexpensive and appeared well tolerated. It is not practice-changing yet: clinician-rated toxicity in a 35-patient unblinded pilot is highly vulnerable to bias and needs confirmation in a multicentre placebo-controlled study.