Efficacy and safety of zinc in the prevention of oral mucositis in children with cancer receiving intensified chemotherapy: A randomized double‐blind placebo‐controlled trial

Abstract

Background and aims A limited number of safe and effective preventive options for oral mucositis (OM) are available. This randomized, double‐blind, placebo‐controlled trial aimed to evaluate the efficacy and safety of zinc in preventing OM in children with cancer receiving intensified chemotherapy. Methods Children aged 3–18 years were randomized to receive oral zinc at 1 mg/kg/dose daily for 14 days or a placebo at the same doses and schedule. The primary outcome of this study was to determine the effect of oral zinc in the prevention of OM, and secondary outcomes included any adverse effect of oral zinc, the severity and duration of OM, and the need for hospitalizations. Results A total of 90 children were randomized to either the oral zinc (n = 44) or placebo group (n = 46). The incidence of OM in the zinc group was 20.5%, while that in the placebo group was 19.6% (p = .91; risk ratio: 1.04, 95% CI 0.45–2.30). There were no significant adverse events of the drug observed. There were no significant differences between the two groups in the severity (p = .79), the mean time of onset (p = .09), the mean duration of OM (p = .18), and the need for hospitalizations (p = 1.0). Conclusions Among children on cancer chemotherapy, there was no decrease in the incidence of OM observed with oral zinc at a dose of 1 mg/kg/day. No significant adverse events were observed with administering oral zinc. Further research is warranted to test higher doses of oral zinc with longer duration for a clinically significant effect.

Oral Mucositis Management in Children under Cancer Treatment: A Systematic Review

“…The articles included in this systematic review described several therapies for oral mucositis management, including the most frequent LLLT [24,30,31,35,43,46,51,56] (20%), followed by palifermin [41,42,44], zinc-containing compounds [33,36,53], honey [21,25,40], calcium phosphate [37,45,49] (8%), olive oil [23,25], oral cryotherapy [38,52], vitamin E [39,57], glutamine [28,59], and chlorhexidine [29,47] (5%) (Figure 2). Interventions that were considered in only one study included Aloe vera [22]; andiroba orabase [55]; bovine colostrum [50]; chewing gum [34]; high-power laser therapy [58]; ketamine [48]; Mucosamin ® oral spray [54]; Mucosyte ® mouthwash [26]; Satureja hortensis gel [27]; transforming growth factor-beta 2 [32]; pycnogenol [39]; and a mixture of honey, olive oilpropolis extract, and beeswax [21].…”

“…The Modified Newcastle-Ottawa Scale, which assesses the quality of study methodology, established high bias in 9 articles [28,29,31,33,38,41,44,47,56] and low bias in 14 articles [21][22][23]25,32,35,42,43,45,48,50,51,53,59]. The remaining articles had moderate bias [24,26,27,30,34,36,37,39,40,46,49,52,54,55,57,58].…”

“…Zinc is a trace metal with antioxidant properties that acts on cell division, tissue repair, immunity, and protein and DNA synthesis [36,53]. There are several zinc supplements, such as zinc gluconate and polaprezinc, but their differences in oral mucositis management remain to be defined [33,36,53].…”

“…Zinc is a trace metal with antioxidant properties that acts on cell division, tissue repair, immunity, and protein and DNA synthesis [36,53]. There are several zinc supplements, such as zinc gluconate and polaprezinc, but their differences in oral mucositis management remain to be defined [33,36,53]. Zinc gluconate was reported to reduce severity, duration, and pain in children with oral mucositis [36]; however, a new study found no effect in the pediatric population [53].…”

“…There are several zinc supplements, such as zinc gluconate and polaprezinc, but their differences in oral mucositis management remain to be defined [33,36,53]. Zinc gluconate was reported to reduce severity, duration, and pain in children with oral mucositis [36]; however, a new study found no effect in the pediatric population [53]. These studies implemented different therapeutic doses of zinc gluconate, 50 mg and 1 mg/kg/day (maximum 30 mg), respectively, and further studies are needed to determine an effective dosage for oral mucositis management in children.…”