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右丙亚胺:关于其在蒽环类化疗期间用于心脏保护的应用综述

Dexrazoxane : a review of its use for cardioprotection during anthracycline chemotherapy.

作者信息

Cvetković Risto S, Scott Lesley J

机构信息

Adis International Limited, Auckland, New Zealand.

出版信息

Drugs. 2005;65(7):1005-24. doi: 10.2165/00003495-200565070-00008.

Abstract

Dexrazoxane (Cardioxane, Zinecard, a cyclic derivative of edetic acid, is a site-specific cardioprotective agent that effectively protects against anthracycline-induced cardiac toxicity. Dexrazoxane is approved in the US and some European countries for cardioprotection in women with advanced and/or metastatic breast cancer receiving doxorubicin; in other countries dexrazoxane is approved for use in a wider range of patients with advanced cancer receiving anthracyclines. As shown in clinical trials, intravenous dexrazoxane significantly reduces the incidence of anthracycline-induced congestive heart failure (CHF) and adverse cardiac events in women with advanced breast cancer or adults with soft tissue sarcomas or small-cell lung cancer, regardless of whether the drug is given before the first dose of anthracycline or the administration is delayed until cumulative doxorubicin dose is > or =300 mg/m2. The drug also appears to offer cardioprotection irrespective of pre-existing cardiac risk factors. Importantly, the antitumour efficacy of anthracyclines is unlikely to be altered by dexrazoxane use, although the drug has not been shown to improve progression-free and overall patient survival. At present, the cardioprotective efficacy of dexrazoxane in patients with childhood malignancies is supported by limited data. The drug is generally well tolerated and has a tolerability profile similar to that of placebo in cancer patients undergoing anthracycline-based chemotherapy, with the exception of a higher incidence of severe leukopenia (78% vs 68%; p < 0.01). Dexrazoxane is the only cardioprotective agent with proven efficacy in cancer patients receiving anthracycline chemotherapy and is a valuable option for the prevention of cardiotoxicity in this patient population.

摘要

右丙亚胺(Cardioxane、Zinecard,乙二胺四乙酸的环状衍生物)是一种位点特异性心脏保护剂,可有效预防蒽环类药物引起的心脏毒性。在美国和一些欧洲国家,右丙亚胺被批准用于接受多柔比星治疗的晚期和/或转移性乳腺癌女性的心脏保护;在其他国家,右丙亚胺被批准用于接受蒽环类药物治疗的更广泛的晚期癌症患者。如临床试验所示,静脉注射右丙亚胺可显著降低晚期乳腺癌女性或软组织肉瘤或小细胞肺癌成人患者中蒽环类药物引起的充血性心力衰竭(CHF)和不良心脏事件的发生率,无论该药物是在蒽环类药物首剂之前给药还是给药延迟至多柔比星累积剂量≥300mg/m²。该药物似乎也能提供心脏保护作用,而与预先存在的心脏危险因素无关。重要的是,尽管尚未证明右丙亚胺能改善无进展生存期和总体患者生存率,但使用右丙亚胺不太可能改变蒽环类药物的抗肿瘤疗效。目前,右丙亚胺在儿童恶性肿瘤患者中的心脏保护疗效的数据有限。该药物一般耐受性良好,在接受基于蒽环类药物化疗的癌症患者中,其耐受性与安慰剂相似,只是严重白细胞减少症的发生率较高(78%对68%;p<0.01)。右丙亚胺是唯一一种在接受蒽环类药物化疗的癌症患者中已证实具有疗效的心脏保护剂,是预防该患者群体心脏毒性的一个有价值的选择。

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