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, Ca2+/Mg2+ 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 Ca2+/Mg2+ 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.