Efficacy of oral and topical antioxidants in the prevention and management of oral mucositis in head and neck cancer patients: a systematic review and meta-analyses

Purpose To evaluate the effectiveness of antioxidants in the prevention and management of oral mucositis in adults undergoing radiotherapy and/or chemotherapy with diagnosed head and neck cancer (HNC) compared to placebo intervention. Methods Cochrane, EMBASE, PubMed, and Web of Science databases were used to search for randomized controlled trials (RCTs) comparing oral or topical antioxidants with placebo in clinically diagnosed HNC adult patients receiving radiotherapy with/without chemotherapy. The primary outcome was to assess the efficacy of the antioxidant to prevent and decrease the incidence/prevalence and severity of oral/oropharyngeal mucositis. The risk of bias was assessed following Cochrane’s guidelines. Results The database search resulted in 203 records up to February 19, 2021. Thirteen RCTs were included with 650 HNC-diagnosed patients. Included studies showed a statistically significant improvement in mucositis severity score for all antioxidants except melatonin. However, further studies are needed as only one study reported outcomes for zinc, propolis, curcumin, and silymarin. Patients receiving vitamin E were 60% less likely to develop severe mucositis grade 2 or higher than those receiving placebo in one study ( P = 0.040). Patients receiving zinc were 95% less likely to develop severe mucositis (grades 3–4) in one study compared to placebo ( P = 0.031). One meta-analysis showed no statistical difference in the risk of having severe mucositis (grades 3–4) with 199 patients compared to placebo for honey ( n = 2 studies, P = 0.403). Meta-analyses could not be conducted for zinc, propolis, curcumin, melatonin, silymarin, and selenium due to the lack of studies reporting similar outcomes for the same intervention. Conclusion Though oral and topical antioxidants significantly improved mucositis severity scores in HNC patients receiving radiotherapy with/without chemotherapy in individual studies, the quality of the evidence was low due to the small number of studies and unclear/high-risk bias. Additionally, large RCTs are needed to confirm these results.