Topical application of honey in the management of chemo/radiotherapy-induced oral mucositis: A systematic review and network meta-analysis.

Background: Mucositis is an inflammatory response of mucosal epithelial cells to the cytotoxic effects of chemotherapy and radiation therapy. To assess the comparative efficacy of honey for patients with cancer undergoing chemo/radiotherapy-induced oral mucositis through a systematic review and network meta-analysis.

Methods: A network meta-analysis was used to identify evidence from relevant randomized controlled trials (RCTs). We searched PubMed, Embase, and the Cochrane Library for publications up to November 2017. The prespecified primary efficacy outcome was the treatment effect of moderate-severe oral mucositis with honey. We performed subgroup analyses and meta-regressions according to the age group, cancer type, mucositis cause, honey type, control arm and type of assessment scale. Moreover, secondary efficacy outcomes were treatment completed, onset time of mucositis, swallowing diary, fungal colonization, bacterial colonisation and analgesic use. And, we did standardize meta-analyses using the random-effects model, later completing the random-effects network meta-analyses by different treatment/control arms.

Results: A total of 17 RCTs were eligible (22 analyses), involving 1265 patients and 13 arms. Honey treatment arm significantly increased the therapeutic effect of chemo/radiotherapy-induced moderate-severe oral mucositis (0.25, 0.14-0.46); significant efficacy was observed in a large proportion of subgroups. The meta-regression may have identified the causes of heterogeneity as the honey type (P = 0.038). Therefore, we need to perform further comparisons of difference in honey types and controls by network meta-analysis, and the results from network meta-analysis revealed that pure natural honey was superior in therapeutic effect (0.05, 0.01-0.46). For secondary outcomes, significant effect was found in decreasing onset time of mucositis (0.41, 0.08-0.73), while no increase in adverse effects was observed. The study is registered with PROSPERO (CRD42017070873).

Conclusions: The adjuvant treatment honey is effective and safe for patients with cancer undergoing chemo/radiotherapy-induced oral mucositis, especially applied pure natural local honey can be invoked as a first-line adjuvant therapy agent.