Topical Esomeprazole for the Prevention and Treatment of Radiation Dermatitis in Patients With Head and Neck Cancer: Protocol for a Phase 2 Randomized Controlled Trial

BACKGROUND: Radiation dermatitis (RD) is a common and clinically significant toxicity affecting the majority of patients undergoing external beam radiation therapy, particularly those treated for head and neck cancer (HNC). RD can impair quality of life, limit treatment intensity, and compromise oncologic outcomes; yet, there is no established standard-of-care for its prevention or management. Preclinical studies suggest that a topically reformulated proton pump inhibitor (PPI), esomeprazole (Dermaprazole), has antioxidant, anti-inflammatory, and antifibrotic properties that may mitigate radiation-induced skin injury. OBJECTIVE: This phase 2 randomized controlled trial aims to evaluate the potential safety, feasibility, and efficacy of prophylactic topical Dermaprazole compared with standard supportive care (Aquaphor) in reducing the incidence and severity of clinically significant RD in patients with HNC receiving definitive chemoradiation. METHODS: This is a prospective, single-center, randomized controlled trial with a 2:1 allocation ratio. A total of 45 adults (≥18 y) with biopsy-confirmed head and neck malignancy planned to receive definitive chemoradiation of at least 66 Gy will be enrolled. Participants will be randomized to receive twice-daily topical Dermaprazole or Aquaphor beginning at computed tomography (CT) simulation and continuing through 2 weeks after completion of radiation therapy. The primary outcome is the rate and severity of RD, assessed weekly during treatment using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5 by the treating radiation oncologist, with blinded dermatologic assessment based on standardized medical photography. Feasibility outcomes include accrual rate, treatment compliance, and questionnaire completion rates. Secondary outcomes include time to onset and healing of grade ≥2 RD, quality of life assessed using the Skindex-16 instrument, radiation dose thresholds associated with dermatitis, and changes in inflammatory biomarkers (C-reactive protein, tumor necrosis factor-α, interleukin [IL]-1β, and IL-6). More specifically, secondary outcomes will be assessed through serial CTCAE version 5 evaluations for onset and healing, Skindex16 questionnaires for quality of life, radiation dose-volume parameters for dermatitis thresholds, and serum inflammatory marker concentration measurements before, during, and after treatment. RESULTS: The study began in June 2022 and has completed enrollment. Data analysis will commence following completion of data collection, with results expected to be published by 2027. CONCLUSIONS: Should Dermaprazole demonstrate efficacy in reducing RD in patients undergoing radiation therapy, it may offer an alternative or adjunctive treatment option for the prevention and management of RD, potentially reducing treatment-related morbidity and improving patients' quality of life during radiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04865731; https://clinicaltrials.gov/study/NCT04865731. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/91035.