Weijl N I, Elsendoorn T J, Lentjes E G W M, Hopman G D, Wipkink-Bakker A, Zwinderman A H, Cleton F J, Osanto S
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
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.
顺铂诱导的毒性主要由自由基的形成引起,导致器官氧化损伤。在癌症患者接受顺铂化疗期间,血浆中抗氧化剂的浓度会显著下降。48名接受基于顺铂化疗的癌症患者被双盲随机分组,分别接受溶解在饮料中的维生素C、维生素E和硒补充剂,或接受安慰剂饮料。主要观察指标是顺铂诱导的肾毒性和耳毒性的程度。在这两个研究组之间,就这些主要观察指标而言,未发现显著差异。然而,血浆中这三种抗氧化微量营养素浓度达到最高的患者,其高音听力损失明显较少。此外,还发现还原型/氧化型维生素C比值与氧化应激标志物丙二醛(MDA)以及顺铂诱导的耳毒性和肾毒性之间存在显著相关性。干预组患者对顺铂诱导的毒性缺乏保护作用,可能与依从性差和/或补充不足有关。应进一步研究更高剂量(强度)的补充剂以及与其他抗氧化剂联合使用的情况。