Effects of different drugs on radiation-induced oral mucositis in patients with head and neck tumors: a systematic review and a network meta-analysis.

BACKGROUND

Radiation-induced oral mucositis (RIOM) affects over 80% of head and neck tumor patients receiving radiotherapy. Although four routine drugs are used for RIOM prevention, direct comparative evidence across multiple clinical outcomes remains insufficient. This study aims to compare the effects of different pharmacological interventions on RIOM in patients with head and neck tumors via a network meta-analysis of RIOM.

METHODS

We conducted systematic searches in PubMed, EMBASE, and the Cochrane Library for RCTs published up to August 31, 2025. The search only included articles in English. We selected studies that reported on the severity of RIOM, the duration of RIOM, the severity of xerostomia, and the severity of dysphagia as primary outcomes. Secondary outcomes included the use of analgesics, weight loss, the use of feeding tubes, and treatment interruptions. We used the Risk-of-Bias 2 (RoB2) tool to assess the risk of bias in the included studies and performed a network meta-analysis by using Stata 17.0 software.

RESULTS

A total of 29 RCTs involving 2,276 patients were included. Glutamine significantly reduced the risk of RIOM compared with amifostine [odds ratio (OR) =0.13, 95% confidence interval (CI): 0.03-0.51] and cytokine (OR =0.31, 95% CI: 0.10-0.99). Compared with amifostine, cytokine (OR: 10.28, 95% CI: 1.09, 96.79), glutamine (OR: 11.09, 95% CI: 1.10, 112.24), and placebo (OR: 12.54, 95% CI: 1.41, 111.20) all significantly increased the number of cases with dysphagia. Glutamine reduced the number of patients requiring feeding tubes and the incidence of treatment interruptions. However, no significant differences were found in the duration of RIOM, the number of reported ≥ grade II xerostomia cases, the number of patients using analgesics, or weight loss.

CONCLUSIONS

Glutamine is recommended as the preferred pharmacological intervention for preventing and alleviating RIOM in head and neck cancer patients, particularly in reducing the risks of severe RIOM, incidence of feeding tube, and treatment interruptions. Additionally, amifostine significantly reduced the risk of dysphagia. Based on the current evidence, glutamine appears to offer the most favorable risk-benefit profile among the evaluated interventions. Future research should adopt well-designed, unified RCTs with adequate samples to revalidate whether these measures are truly effective and safe.