Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: a randomized double-blind placebo controlled trial

Zohreh Ghoreishi, Ali Esfahani, Abolghasem Djazayeri, Mahmoud Djalali, Banafsheh Golestan, Hormoz Ayromlou, Shahriar Hashemzade, Mohammad Asghari Jafarabadi, Vahid Montazeri, Seyed Ali Keshavarz, Masoud Darabi, Zohreh Ghoreishi, Ali Esfahani, Abolghasem Djazayeri, Mahmoud Djalali, Banafsheh Golestan, Hormoz Ayromlou, Shahriar Hashemzade, Mohammad Asghari Jafarabadi, Vahid Montazeri, Seyed Ali Keshavarz, Masoud Darabi

Abstract

Background: Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy.

Methods: This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN). Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on "reduced Total Neuropathy Score".

Results: Twenty one patients (70%) of the group taking omega-3 fatty acid supplement (n = 30) did not develop PN while it was 40.7%( 11 patients) in the placebo group(n = 27). A significant difference was seen in PN incidence (OR = 0.3, .95% CI = (0.10-0.88), p = 0.029). There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95% CI = (-2.06 -0.02), p = 0.054).

Conclusions: Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients' quality of life.

Trial registration: This trial was registered at ClinicalTrials.gov (NCT01049295).

Figures

Figure 1
Figure 1
Flow diagram of the study design.

References

    1. Hagiwara H, Sunada Y. Mechanism of taxane neurotoxicity. Breast Cancer. 2004;11(1):82–85. doi: 10.1007/BF02968008.
    1. Chaudhry V, Rowinsky EK, Sartorius SE, Donehower RC, Cornblath DR. Peripheral neuropathy from taxol and cisplatin combination chemotherapy: clinical and electrophysiological studies. Ann Neurol. 1994;35(3):304–311. doi: 10.1002/ana.410350310.
    1. Kuroi K, Shimozuma K. Neurotoxicity of taxanes: symptoms and quality of life assessment. Breast Cancer. 2004;11(1):92–99. doi: 10.1007/BF02968010.
    1. Stillman M, Cata JP. Management of chemotherapy-induced peripheral neuropathy. Curr Pain Headache Rep. 2006;10(4):279–287. doi: 10.1007/s11916-006-0033-z.
    1. Shapiro H. Could n-3 polyunsaturated fatty acids reduce pathological pain by direct actions on the nervous system? Prostaglandins Leukot Essent Fatty Acids. 2003;68(3):219–224. doi: 10.1016/S0952-3278(02)00273-9.
    1. Mazza M, Pomponi M, Janiri L, Bria P, Mazza S. Omega-3 fatty acids and antioxidants in neurological and psychiatric diseases: an overview. In., vol. 31. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(1):12–26. doi: 10.1016/j.pnpbp.2006.07.010. Epub 2006 Aug 28.
    1. Coste TC, Gerbi A, Vague P, Pieroni G, Raccah D. Neuroprotective effect of docosahexaenoic acid-enriched phospholipids in experimental diabetic neuropathy. Am Diabetes Assoc. 2003;52:2578.
    1. Cavaletti G, Bogliun G, Marzorati L, Zincone A, Piatti M, Colombo N, Parma G, Lissoni A, Fei F, Cundari S. et al.Grading of chemotherapy-induced peripheral neurotoxicity using the Total Neuropathy Scale. Neurology. 2003;61(9):1297–1300. doi: 10.1212/01.WNL.0000092015.03923.19.
    1. Ocean AJ, Vahdat LT. Chemotherapy-induced peripheral neuropathy: pathogenesis and emerging therapies. Support Care Cancer. 2004;12(9):619–625.
    1. Kimura J. Electrodiagnosis in diseases of nerve and muscle, principles and practice. 3. Oxford University Press ; 2001.
    1. Noori M, Darabi M, Rahimipour A, Rahbani M, Abadi NA, Darabi M, Ghatrehsamani K. Fatty acid composition of HDL phospholipids and coronary artery disease. J Clin Lipidol. 2009;3(1):39–44. doi: 10.1016/j.jacl.2008.11.010.
    1. Pocock SJ. Clinical Trials: A Practical Approach. John Wiley & Sons ; 1983.
    1. Okuda Y, Mizutani M, Ogawa M, Sone H, Asano M, Asakura Y, Isaka M, Suzuki S, Kawakami Y, Field JB. Long-term effects of eicosapentaenoic acid on diabetic peripheral neuropathy and serum lipids in patients with type II diabetes mellitus. In., vol. 10. Elsevier ; 1996. pp. 280–287.
    1. Taxol Prescribing Information. Bristol Meyers Squibb. Available at . Accessed April 13,2005.
    1. Head KA. Peripheral neuropathy: pathogenic mechanisms and alternative therapies. Altern Med Rev. 2006;11(4):294–329.
    1. Gerbi A, Maixent JM, Ansaldi JL, Pierlovisi M, Coste T, Pelissier JF, Vague P, Raccah D. Fish oil supplementation prevents diabetes-induced nerve conduction velocity and neuroanatomical changes in rats. Am Soc Nutrition. 1999;129:207.
    1. Mielke S, Sparreboom A, Mross K. Peripheral neuropathy: a persisting challenge in paclitaxel-based regimes. Eur J Cancer. 2006;42(1):24–30. doi: 10.1016/j.ejca.2005.06.030.
    1. Argyriou AA, Polychronopoulos P, Koutras A, Iconomou G, Iconomou A, Kalofonos HP, Chroni E. Peripheral neuropathy induced by administration of cisplatin- and paclitaxel-based chemotherapy. Could it be predicted? Support Care Cancer. 2005;13(8):647–651. doi: 10.1007/s00520-005-0776-9.
    1. Visovsky C, Collins M, Abbott L, Aschenbrenner J, Hart C. Putting evidence into practice: evidence-based interventions for chemotherapy-induced peripheral neuropathy. Clin J Oncol Nurs. 2007;11(6):901–913. doi: 10.1188/07.CJON.901-913.
    1. Lauretani F, Bandinelli S, Benedetta B, Cherubini A, Iorio AD, Ble A, Giacomini V, Corsi AM, Guralnik JM, Ferrucci L. Omega-6 and omega-3 fatty acids predict accelerated decline of peripheral nerve function in older persons. In., vol. 14. Wiley Online Library ; 2007. pp. 801–808.
    1. Ward RE, Huang W, Hall JCE, Priestley JV, Michael-Titus AT. Effect of docosahexaenoic acid on axonal damage after spinal cord injury. In., vol. 14. 2007.
    1. Wolff AC, Donehower RC, Carducci MK, Carducci MA, Brahmer JR, Zabelina Y, Bradley MO, Anthony FH, Swindell CS, Witman PA. et al.Phase I study of docosahexaenoic acid-paclitaxel: a taxane-fatty acid conjugate with a unique pharmacology and toxicity profile. Clin Cancer Res. 2003;9(10 Pt 1):3589–3597.
    1. Ocean AJ, Vahdat LT. Chemotherapy-induced peripheral neuropathy: pathogenesis and emerging therapies. In., vol. 12. Springer ; 2004. pp. 619–625.
    1. Curtis CL, Hughes CE, Flannery CR, Little CB, Harwood JL, Caterson B. n-3 fatty acids specifically modulate catabolic factors involved in articular cartilage degradation. J Biol Chem. 2000;275(2):721–724. doi: 10.1074/jbc.275.2.721.
    1. Lee JH, O'Keefe JH, Lavie CJ, Marchioli R, Harris WS. Omega-3 fatty acids for cardioprotection. Mayo Clinic. 2008;83:324–332. doi: 10.4065/83.3.324.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren