Prevention of oxaliplatin-related neurotoxicity by ω-3 PUFAs: A double-blind randomized study of patients receiving oxaliplatin combined with capecitabine for colon cancer

Medicine (Baltimore). 2020 Dec 11;99(50):e23564. doi: 10.1097/MD.0000000000023564.

Abstract

Background: Peripheral neurotoxicity (PN) is a frequent side effect of oxaliplatin treatment, and also is its dose-limiting toxicity. Studies have confirmed that ω-3 polyunsaturated fatty acids (ω-3 PUFAs) had a neuroprotective effect. However, the efficacy of ω-3 PUFAs on the prevention of oxaliplatin-related neurotoxicity remains unclear. We assessed the effect of ω-3 PUFAs on the neurotoxicity in colon cancer patients treated by oxaliplatin combined with capecitabine.

Methods: In a randomized, double-blind, placebo-controlled study, 179 patients with colon cancer receiving oxaliplatin combined with capecitabine were recruited, and randomly assigned to take ω-3 PUFAs, 640 mg t.i.d during chemotherapy and 1 month after the end of the treatment or placebo. All patients were treated with chemotherapy for 6 treatment cycles. The incidence and severity of PN were evaluated, and the nerve conduction was measured before the onset of chemotherapy and 1 month after treatment. In addition, the quality of life was also accessed using Chinese version of European organization for research and treatment of cancer quality of life questionnaire.

Results: The incidence of PN in the ω-3 PUFAs group and placebo group was 52.22% and 69.66%, respectively (P = .017). In addition, there was a significant difference in the severity of PN between the 2 groups (P = .017). In terms of motor and sensory nerve conduction, the sensory action potentials amplitude of sural nerve in the ω-3 PUFAs group and placebo group after chemotherapy treatment were (15.01 ± 3.14) and (13.00 ± 3.63) μ V respectively, suggesting there was a significant difference in the 2 groups (P = .000). In addition, the mean score of the global health-status/quality of life was obviously higher in the ω-3 PUFAs group than that in the placebo group.

Conclusion: ω-3 PUFAs seem to reduce the incidence and severity of oxaliplatin-related neurotoxicity, and improve the quality of patients' life, indicating it is expected to be a potential drug for the treatment of oxaliplatin-related neurotoxicity.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Capecitabine / administration & dosage
  • Capecitabine / therapeutic use*
  • Colonic Neoplasms / drug therapy*
  • Double-Blind Method
  • Drug Administration Schedule
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / therapeutic use*
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / prevention & control*
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / therapeutic use
  • Oxaliplatin / toxicity*
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / prevention & control
  • Quality of Life
  • Surveys and Questionnaires

Substances

  • Fatty Acids, Omega-3
  • Neuroprotective Agents
  • Oxaliplatin
  • Capecitabine