A multicenter randomized phase II trial of topical betamethasone ointment for preventing severe chemoradiotherapy-induced oral mucositis in head and neck cancer.

12015 Background: Severe oral mucositis (OM) is a major unmet clinical problem during cisplatin-based chemoradiotherapy (CRT) for head and neck cancer, with no established preventive strategy. Although topical dexamethasone has shown benefit during radiotherapy alone, its efficacy during CRT is limited. This study represents the first randomized trial evaluating a potent topical corticosteroid, betamethasone ointment, for preventing severe OM during cisplatin-based CRT. Methods: Patients with head and neck cancer receiving CRT with the oral cavity included in the radiation field were enrolled at six institutions in Japan. Upon development of grade 1 OM (CTCAE v5.0), patients were randomized to standard oral care alone (control) or standard oral care plus topical betamethasone ointment applied three times daily (intervention). Treatment continued until completion of radiotherapy or onset of grade 3 OM. The primary endpoint was time to grade 3 OM, analyzed using multivariable Cox proportional hazards models. Secondary endpoints included time to grade 2/3 OM and incidence of oral candidiasis. Results: A total of 68 patients were analyzed (intervention n=35; control n=33). The cumulative incidence of grade 3 OM was significantly lower in the intervention group (14.3%) than in the control group (48.5%). Topical betamethasone significantly reduced the risk of grade 3 OM (HR 0.246, 95% CI 0.081–0.749). Betamethasone also delayed the onset of grade 2/3 OM. Non-use of a spacer was independently associated with grade 2 OM. Betamethasone did not increase oral candidiasis, whereas denture use was a significant risk factor. Conclusions: Topical betamethasone ointment substantially reduced the incidence of severe OM during cisplatin-based CRT without increasing oral candidiasis. This simple, low-cost, and widely accessible intervention could be rapidly implemented in routine clinical practice to mitigate CRT-induced toxicity. To our knowledge, this is the first randomized trial demonstrating the efficacy of a potent topical corticosteroid for preventing severe OM during cisplatin-based CRT. Clinical trial information: jRCTs071200013.