The Efficacy and Safety of Antifungal Agents for Managing Oral Candidiasis in Oncologic Patients: A Systematic Review With Network Meta-Analysis

This study aimed at synthesizing the available evidence on the comparative safety and efficacy of antifungal agents for preventing or treating oral candidiasis (OC) in oncologic patients. A systematic review following international recommendations was performed (PROSPERO CRD42024507745). A comprehensive search was conducted in PubMed, Scopus, and Web of Science (Feb 2024) to retrieve randomized controlled trials evaluating the clinical effects of antifungal agents in the management of OC in this vulnerable population. Network meta-analyses were performed to evaluate the most prevalent outcomes, with findings reported as odds ratios (ORs) with 95% confidence intervals (CIs). Overall, 24 trials were included, of which 10 addressed OC treatment and 14 disease prophylaxis (n=3449 patients). Fluconazole had the most significant rates of clinical cure when compared to placebo (OR 0.09 [95% CI 0.01-0.69]), amphotericin B (0.21 [95% CI 0.07-0.65]) and itraconazole (OR 0.58 [95% CI 0.34-0.99]); ketoconazole was also superior to placebo for this outcome (OR 0.10 [95% CI 0.03, 0.36]). All antifungal agents presented significantly higher rates of prophylaxis success compared to the absence of an active agent. While these therapies were generally considered safe, only four studies provided data on adverse events, primarily related to gastrointestinal issues. In oncologic patients, azoles (fluconazole, ketoconazole) should be used as a first-line approach for OC treatment. The selection of antifungal agents for disease prophylaxis should consider, among others, patients' clinical characteristics and preferences. Economic and quality of life-related outcomes should be further addressed in future studies.