Supportive Care in Cancer

, Volume 14, Issue 11, pp 1134–1140 | Cite as

A randomized controlled trial evaluating the efficacy and safety of vitamin E supplementation for protection against cisplatin-induced peripheral neuropathy: final results

  • Andreas A. Argyriou
  • Elisabeth ChroniEmail author
  • Angelos Koutras
  • Gregoris Iconomou
  • Spiridon Papapetropoulos
  • Panagiotis Polychronopoulos
  • Haralabos P. Kalofonos
Original Article



A randomized, open label with blind assessment, controlled trial was performed to assess efficacy and adverse-event profile of vitamin E, given as supplementation for prophylaxis against cisplatin-induced peripheral neuropathy (CIPN).

Patients and methods

A total of 30 patients scheduled to receive six courses of cumulative cisplatin-based regimens were randomly allocated to treatment and control groups and were then studied by means of neurological examination and electrophysiological study. Patients assigned to group I (n=14) orally received vitamin E at a daily dose of 600 mg/day during chemotherapy and 3 months after its cessation were compared to patients of group II (n=16), who received no vitamin E supplementation and served as controls. The severity of neurotoxicity was summarized by means of a modified Peripheral Neuropathy (PNP) score.


The incidence of neurotoxicity differed significantly between groups, occurring in 3/14 (21.4%) of patients assigned to the vitamin E supplementation group and in 11/16 (68.5%) of controls (p=0.026). The relative risk (RR) of developing neurotoxicity was significantly higher in case of controls, RR=2.51, 95% C.I.=1.16–5.47. Mean PNP scores were 4.99±1.33 for patients of group I and 10.47±10.62 for controls, (p=0.023). None of the adverse events or deaths occurred, were judged as likely to be related to the vitamin E supplementation.


Vitamin E effectively and safely protects patients with cancer from occurrence of cisplatin neurotoxicity.


Cisplatin Peripheral neuropathy Vitamin E Neuroprotection 


Conflict of interest

We have no conflict of interest.


  1. 1.
    Alberts DS, Noel JK (1995) Cispaltin-associated neurotoxicity: can it be prevented? Anticancer Drugs 6:369–383CrossRefPubMedGoogle Scholar
  2. 2.
    Argyriou AA, Chroni E, Koutras A, Ellul J, Papapetropoulos S, Katsoulas G, Iconomou G, Kalofonos HP (2005) Vitamin E for prophylaxis against chemotherapy-induced neuropathy: a randomized controlled trial. Neurology 64(1):26–31PubMedGoogle Scholar
  3. 3.
    Berger T, Malayeri R, Doppelbauer A, Krajnik G, Huber H, Auff E, Pirker R (1997) Neurological monitoring of neurotoxicity induced by paclitaxel/cisplatin chemotherapy. Eur J Cancer 33(9):1393–1399CrossRefPubMedGoogle Scholar
  4. 4.
    Bove L, Picardo M, Maresca V, Jandolo B, Pace A (2001) A pilot study on the relationship between cisplatin neuropathy and vitamin E. J Exp Clin Cancer Res 20(2):277–280PubMedGoogle Scholar
  5. 5.
    Brigelius-Flohe R, Kelly FJ, Salonen JT, Neuzil J, Zingg JM, Azzi A (2002) The European perspective on vitamin E: current knowledge and future research. Am J Clin Nutr 76(4):703–716PubMedGoogle Scholar
  6. 6.
    Chaudhry V, Rowinsky EK, Sartorius SE, Donehower RC, Cornblath DR (1994) Peripheral neuropathy from taxol and cisplatin combination chemotherapy: Clinical and electrophysiological studies. Ann Neurol 35:304–311CrossRefPubMedGoogle Scholar
  7. 7.
    Dyck PJ, Thomas PK (eds) (1993) Peripheral neuropathy, vol 2, 3 edn. WB Saunders, Philadelphia, PA, pp 1310–1317Google Scholar
  8. 8.
    Gregg RW, Molepo JM, Monpetit VJ, Mikael NZ, Redmond D, Gadia M, Stewart DJ (1992) Cisplatin neurotoxicity: the relationship between dosage, time, and platinum concentration in neurological tissue and morphological evidence of toxicity. J Clin Oncol 10:795–803PubMedGoogle Scholar
  9. 9.
    Halliwell B, Gutteridge JMC (1993) Free radicals in biology and medicine. Oxford University Press, Oxford, pp 188–276Google Scholar
  10. 10.
    Hathcock JN, Azzi A, Blumberg J et al (2005) Vitamins E and C are safe across a broad range of intakes. Am J Clin Nutr 81(4):736–745PubMedGoogle Scholar
  11. 11.
    Kimura J (2001) Electrodiagnosis in diseases of nerve and muscle, principles and practice, 3rd edn. Oxford University press, pp 91–166Google Scholar
  12. 12.
    Kleyweg RP, Van der Meché FGA, Schmitz PIM (1991) Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain–Barré syndrome. Muscle Nerve 14:1103–1109CrossRefPubMedGoogle Scholar
  13. 13.
    Ko HY, Park-Ko I (1999) Electrophysiologic recovery after vitamin E-deficient neuropathy. Arch Phys Med Rehabil 80(8):964–967CrossRefPubMedGoogle Scholar
  14. 14.
    Leonetti C, Biroccio A, Gabellini C et al (2003) Alpha-tocopherol protects against cisplatin-induced toxicity without interfering with antitumor efficacy. Int J Cancer 104(2):243–250CrossRefPubMedGoogle Scholar
  15. 15.
    Manzella D, Barbieri M, Ragno E, Paolisso G (2001) Chronic administration of pharmacologic doses of vitamin E improves the cardiac autonomic nervous system in patients with type 2 diabetes. Am J Clin Nutr 73:1052–1057PubMedGoogle Scholar
  16. 16.
    Miller ER 3rd, Pastor-Barriuso R, Dalal D et al (2005) Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142(1):37–46PubMedGoogle Scholar
  17. 17.
    Morinobu T, Ban R, Yoshikawa S, Murata T, Tamai H (2002) The safety of high dose vitamin E supplementation in healthy Japanese male adults. J Nutr Sci Vitaminol 48(1):6–9PubMedGoogle Scholar
  18. 18.
    Pace A, Savarese A, Picardo M, Maresca V, Pacetti U, Del Monte G, Biroccio A, Leonetti C, Jandolo B, Cognetti F, Bove L (2003) Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. J Clin Oncol 21(5):927–931CrossRefPubMedGoogle Scholar
  19. 19.
    Panayiotopoulos CP, Chroni E (1996) F-waves in clinical neurophysiology: a review. Methodological issues and overall value in peripheral neuropathies. Electroencephalogr Clin Neurophysiol 101:365–374PubMedGoogle Scholar
  20. 20.
    Park SA, Choi KS, Bang JH, Huh K, Kim SU (2000) Cisplatin-induced apoptotic cell death in mouse hybrid neurons is blocked by antioxidants through suppression of cisplatin-mediated accumulation of p53 but not of Fas/Fas ligand. J Neurochem 75(3):946–953CrossRefPubMedGoogle Scholar
  21. 21.
    Peltier AC, Russell JW (2002) Recent advances in drug-induced neuropathies. Curr Opin Neurol 15(5):633–638CrossRefPubMedGoogle Scholar
  22. 22.
    Satya-Murti S, Howard L, Krohel G, Wolf B (1986) The spectrum of neurological disorder from vitamin E deficiency. Neurology 36:917–921PubMedGoogle Scholar
  23. 23.
    Traber MG, Sokol RJ, Ringel SP, Neville HE, Thellman CA, Kayden HJ (1987) Lack of a-tocopherol in peripheral nerves of vitamin E patients with peripheral neuropathy. N Engl J Med 317:262–285PubMedCrossRefGoogle Scholar
  24. 24.
    Weijl NI, Hopman GD, Wipkink-Bakker A, Lentjes EG, Berger HM, Cleton FJ, Osanto S (1998) Cisplatin combination chemotherapy induces a fall in plasma antioxidants of cancer patients. Ann Oncol 9(12):1331–1337CrossRefPubMedGoogle Scholar
  25. 25.
    Windebank AJ (1999) Chemotherapeutic neuropathy. Curr Opin Neurol 12:565–571CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Andreas A. Argyriou
    • 1
  • Elisabeth Chroni
    • 1
    • 3
    Email author
  • Angelos Koutras
    • 2
  • Gregoris Iconomou
    • 2
  • Spiridon Papapetropoulos
    • 1
  • Panagiotis Polychronopoulos
    • 1
  • Haralabos P. Kalofonos
    • 2
  1. 1.EMG/ENG Laboratory, Department of NeurologyUniversity of Patras Medical SchoolRion-PatrasGreece
  2. 2.Division of Oncology, Department of MedicineUniversity of Patras Medical SchoolRion-PatrasGreece
  3. 3.Neurology DepartmentUniversity of Patras Medical SchoolRion-PatrasGreece

Personalised recommendations