SYSTEMATIC REVIEW article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1642552
Anti-oxidative stress therapies prevent severe chemotherapy-induced peripheral neuropathy in colorectal cancer patients treated with oxaliplatin: a systematic review and meta-analysis
Provisionally accepted
Mohamed Salama
David BarnesAnni GeorghiouMariam Murad
Seham Almalki
Zubair Ahmed*Mark R Openshaw*
Claire Palles*
Richard Tuxworth*- University of Birmingham, Birmingham, United Kingdom
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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.
Keywords: bowel cancer, CIPN, platinum agents, Neurotoxicity, Oxidative Stress, Mitochondrial dysfunction
Received: 06 Jun 2025; Accepted: 15 Aug 2025.
Copyright: © 2025 Salama, Barnes, Georghiou, Murad, Almalki, Ahmed, Openshaw, Palles and Tuxworth. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zubair Ahmed, University of Birmingham, Birmingham, United Kingdom
Mark R Openshaw, University of Birmingham, Birmingham, United Kingdom
Claire Palles, University of Birmingham, Birmingham, United Kingdom
Richard Tuxworth, University of Birmingham, Birmingham, United Kingdom
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