The efficacy and safety of calmangafodipir in preventing chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis.

Abstract

e24208 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent, dose-limiting toxicity of oxaliplatin-based chemotherapy with significant impact on quality of life and treatment delivery. Calmangafodipir (CaM), a manganese-containing superoxide dismutase mimetic, has been investigated as a potential neuroprotective agent to prevent CIPN. This study is being done to assess the efficacy and safety of Calmangafodipir in preventing chemotherapy-induced peripheral neuropathy. Methods: A systematic search of Cochrane Central, PubMed, ScienceDirect, Scopus, and Google Scholar from inception to January 2026 identified randomized controlled trials evaluating CaM versus placebo in patients receiving chemotherapy. Eligible studies enrolled human subjects undergoing chemotherapy, compared CaM with placebo, and reported CIPN outcomes and/or adverse events. Data were pooled using random-effects models; risk ratios (RR) or odds ratios (OR) with 95% confidence intervals (CI) were calculated, and heterogeneity was assessed with the I 2 statistic. Results: Of 238 records screened, 4 RCTs met inclusion criteria. At 9 months, CaM was associated with a significantly higher risk of CIPN compared with placebo (RR 1.37, 95% CI 1.10–1.70, p = 0.004; I 2 = 0). At 4 months, there was no significant difference in CIPN risk between CaM and placebo (HR 0.60, 95% CI 0.34–1.05, p = 0.07; I 2 = 0). There was no statistically significant difference in overall adverse events for CaM 2 versus placebo (OR 0.61, 95% CI 0.17–2.11, p = 0.43; I 2 = 0) or treatment-emergent serious adverse events for CaM 5 versus placebo (OR 1.91, 95% CI 0.36–10.20, p = 0.45; I 2 = 78%). Conclusions: In this meta-analysis of randomized trials, calmangafodipir did not prevent chemotherapy-induced peripheral neuropathy and was associated with a higher long-term CIPN risk at 9 months compared with placebo. While overall toxicity and serious adverse events were not significantly different between groups, these findings do not support the use of calmangafodipir as a preventive strategy for CIPN and highlight the need for alternative neuroprotective approaches.