Oral Zinc Sulfate for Prevention and Treatment of Chemotherapy-Induced Oral Mucositis: A Meta-Analysis of Five Randomized Controlled Trials

Abstract

Chemotherapy-induced oral mucositis is an extremely serious complication faced by cancer patients. The role of oral zinc sulfate in preventing and treating chemotherapy-induced oral mucositis remains a subject of debate. The aim of this systematic review is to assess the potential of oral zinc sulfate to alleviate this morbid condition. A systematic search was conducted electronically in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) to capture all potential randomized controlled trials investigating efficacy and safety of oral zinc sulfate in prevention and treatment of chemotherapy-induced oral mucositis, and the retrieval time was limited from their inception to April 2018. We assigned two independent investigators to perform a search, screen citations, extract information, and evaluate the risk of bias in all included trials. Subsequently, the RevMan 5.3 software was utilized to perform all statistical analyses. We included five eligible studies involving 352 patients. Meta-analysis based on limited data revealed that oral zinc sulfate failed to decrease the incidence of chemotherapy-induced oral mucositis (RR [relative risk] = 0.52, 95% CI [confidence interval] = 0.17–1.64) as well as relieve chemotherapy-induced oral mucositits grade (RR = 0.62, 95% CI = 0.11–3.56; RR = 0.70, 95% CI = 0.29–1.71). Moreover, qualitative analyses also suggested that oral zinc sulfate was not associated with reduced oral pain intensity, delayed onset of chemotherapy-induced oral mucositis, decreased adverse events, or improved quality of life compared with control regimes. Oral zinc sulfate may not provide clinical benefits in preventing or reducing incidence, severity, or pain intensity of chemotherapy-induced oral mucositis in cancer patients. However, more studies with large-scale and rigorous methods are warranted for the purpose of further investigating efficacy and safety of oral zinc sulfate for this pathologic condition due to the presence of limitations.

Prophylaxis With Oral Zinc Sulfate Against Radiation Induced Oral Mucositis in Patients With Head and Neck Cancers: A Systematic Review and Meta-Analysis of Four Randomized Controlled Trials

“…In the current study, incidence of radiation-induced oral mucositis was defined as the value of a number of oral mucositis cases, irrespective of grade, divided by the total number of cancer patients completing the whole study (25). The grade of oral mucositis was evaluated with a scoring system released by the Radiation Therapy Oncology Group (RTOG) or the Oral Mucositis Assessment Scale (OMAS) (26, 27).…”

“…Two independent reviewers were assigned to determine the bias risk from the following seven domains, including randomization sequence generation, allocation concealment, blinding of participants, blinding of study personnel, blinding of outcome assessors, incomplete outcome data, selective reporting, and other biases using the Cochrane risk of bias assessment tool (30, 31). The overall quality of the methodology of an individual study was graded according to the matched level between the actual information and the evaluation criteria (25). A third investigator was invited to solve any discrepancies between the two reviewers.…”

“…More importantly, the incidence of oral mucositis increases to 90% when patients underwent concurrent chemotherapy (7). Head and neck cancer patients with oral mucositis, experience several distressing symptoms such as pain, as well as eating and swallowing difficulties (8) and more importantly, all symptoms related to oral mucositis will also worsen quality of life (QoL) (9, 10) and eventually alter the radiotherapy scheme (11, 12). Therefore, medical prophylaxis methods and treatment of radiation-induced oral mucositis have been explored, such as several organic products and low-level laser therapy (13).…”

Zinc Adequacy Is Essential for the Maintenance of Optimal Oral Health

“…In 2018, a meta-analysis of five randomized controlled trials did not find any beneficial effects of oral zinc sulfate on chemotherapy-induced oral mucositis. They found that oral zinc sulfate may not produce any clinical effects either in preventing or reducing the incidence, alleviating pain intensity, or reducing the severity of chemotherapy-induced oral mucositis [41]. In a randomized trial including leukemia patients undergoing chemotherapy to investigate whether zinc prevented chemotherapy-induced oral mucositis, supplementation with zinc sulfate for a month was not found to be associated with decreased pain intensity [42].…”

Effect of zinc on oropharyngeal mucositis in children with acute leukemia undergoing chemotherapy

“…Patients who also present with neutropenia and thrombocytopenia have an increased risk of oral bleeding and infections, which can lead to septicemia ( 2 , 7 - 9 ). OM involves pain, difficulty in swallowing and speaking, malnutrition, functional status deterioration, longer hospital stay, increased economic costs and decreased quality of life ( 3 , 4 , 7 , 8 , 10 - 13 ). In the pathophysiology of OM, 5 phases have been described in which a variety of cells are involved ( 12 - 14 ).…”