Clinical evidence for managing radiotherapy-induced oral mucositis and xerostomia in head and neck cancer patients: a review of Phase III-IV trials.

Oral Mucositis and xerostomia are common debilitating side effects of radiotherapy in head and neck cancer patients, leading to treatment interruptions and negatively impacting quality of life. This review was performed to examine the efficacy and safety of interventions for managing these complications, evaluated in completed Phase III and IV clinical trials registered on ClinicalTrials.gov. A range of pharmacological and non-pharmacological therapies were reviewed, with analysis of intervention types, outcomes, and sample sizes. For oral mucositis, effective pharmacological agents included palifermin, avasopasem manganese, doxepin, morphine mouthwash, and gabapentin, while non-pharmacological options such as low-level laser therapy, honey, and Aloe vera showed additional benefit in reducing severity and improving healing. In managing radiotherapy-induced xerostomia, pilocarpine, amifostine, and cevimeline significantly enhanced salivary function, with adaptive radiotherapy techniques offering protective effects on the salivary glands. Phase IV studies supported the role of benzydamine, MuGard, Biotène, and herbal mouthwashes in symptom relief and patient comfort. Although several interventions demonstrated promising clinical efficacy, the heterogeneity in study design, outcome measures, and follow-up duration limits definitive conclusions. Therefore, customized, evidence-driven approaches informed by existing recommendations and developed data are crucial for enhancing outcomes and reducing the burden of therapy-induced toxicities in head and neck cancer patients.