Supplementation with antioxidant micronutrients and chemotherapy-induced toxicity in cancer patients treated with cisplatin-based chemotherapy: a randomised, double-blind, placebo-controlled study

Eur J Cancer. 2004 Jul;40(11):1713-23. doi: 10.1016/j.ejca.2004.02.029.


Cisplatin-induced toxicities are mainly caused by the formation of free radicals, leading to oxidative organ damage. Plasma concentrations of antioxidants decrease significantly during cisplatin chemotherapy for cancer. Forty-eight cancer patients treated with cisplatin-based chemotherapy were randomised in a double-blind manner to receive either supplementation with vitamin C, vitamin E and selenium dissolved in a beverage or to receive a placebo beverage. Primary outcome measures were the amount of nephrotoxicity and ototoxicity induced by cisplatin. No significant differences were found between the two study groups with respect to these primary outcome measures. However, patients who achieved the highest plasma concentrations of the three antioxidant micronutrients had significantly less loss of high-tone hearing. In addition, significant correlations were found between the reduced/oxidised vitamin C ratio and malondialdehyde (MDA), markers of oxidative stress, and cisplatin-induced ototoxicity and nephrotoxicity. The lack of protection against cisplatin-induced toxicities in patients in the intervention arm may be related to poor compliance and/or inadequate supplementation. Supplementation with a higher dose (intensity) and in combination with other antioxidants should be investigated further.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Antioxidants / administration & dosage*
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / blood
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects*
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Malondialdehyde / blood
  • Micronutrients / administration & dosage*
  • Middle Aged
  • Neoplasms / drug therapy*
  • Selenium / administration & dosage
  • Selenium / blood
  • Vitamin E / administration & dosage
  • Vitamin E / blood


  • Antineoplastic Agents
  • Antioxidants
  • Micronutrients
  • Vitamin E
  • Malondialdehyde
  • Selenium
  • Ascorbic Acid
  • Cisplatin