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

Background and purpose Chemotherapy-induced peripheral neuropathy (CIPN) is a major side-effect of many commonly used cancer drugs, affecting up to 90% of patients treated with oxaliplatin. This systematic review and meta-analysis analysed randomised controlled trials (RCTs) to determine if any pharmacological agents or traditional medicines can prevent oxaliplatin-induced peripheral neuropathy (OIPN) in colorectal cancer (CRC) patients. Materials and methods We 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. Results 20 studies were included in the systematic review with a median sample size of 61 (range 14-2450). Meta-analysis was conducted for two treatments: first, agents with anti-oxidative stress properties and second, Ca 2+ /Mg 2+ infusions. Anti-oxidative stress treatments were associated with a significant reduction of grade ≥2 OIPN at the end of treatment (OR:0.04, 95%CI:0.01-0.12; p<0.00001). No reduction of grade ≥2 OIPN was observed for Ca 2+ /Mg 2+ infusions. 35% of studies had potential high risk of bias and 45% of studies showed low risk of bias. Conclusions Whilst the existing published RCTs included small numbers of patients, the meta-analysis indicates that anti-oxidative stress therapies can prevent severe OIPN developing at the end of treatment in CRC patients. A large, randomised, placebo-controlled trial assessing OIPN using CTCAE grades and patient-reported outcomes is warranted to confirm these findings.