Anti-oxidative stress therapies reduce chemotherapy-induced peripheral neuropathy in colorectal cancer patients treated with oxaliplatin: a systematic review and meta-analysis

Background and PurposeChemotherapy-induced peripheral neuropathy (CIPN) is a major side-eaect of many commonly used cancer drugs, aaecting up to 90% of patients treated with oxaliplatin. This systematic review and meta-analysis aimed to analyse randomised controlled trials (RCTs) to determine if any pharmacological agents can prevent or reduce oxaliplatin-induced peripheral neuropathy (OIPN) in colorectal cancer (CRC) patients. Materials and MethodsWe searched PubMed, EMBASE and Web of Science for RCTs published before March 2025 that included patients with CRC who received oxaliplatin-based chemotherapy and had peripheral neuropathy quantified using Common Toxicity Criteria for Adverse Events (CTCAE). Meta-analysis was performed for agents tested in three or more RCTs with a minimum combined sample size of 100 patients. Results20 studies were included with a median sample size of 61 (range 14-2450). Meta-analysis was used for two treatments. Anti-oxidative stress treatments were not associated with reduced incidence of grade [&ge;]2 OIPN when assessed mid-treatment but were associated with a significant reduction of grade [&ge;]2 OIPN at the end of treatment (OR:0.04, 95%CI:0.01-0.12; p<0.00001). No reduction of grade [&ge;]2 OIPN was observed for Ca2+/Mg2+ infusions. 35% of studies had potential high risk of bias and 45% of studies showed low risk of bias. ConclusionsWhilst the existing published RCTs included small numbers of patients, the meta-analysis indicates that anti-oxidative stress therapies reduce the end of treatment severe OIPN incidence in CRC patients. A large, randomised, placebo-controlled trial assessing OIPN using CTCAE grades and patient-reported outcomes is warranted to confirm these findings.