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接受癌症药物治疗的患者中的肾病——铂类衍生物(顺铂和卡铂)

[Nephropathy in Patients Undergoing Cancer Drug Therapy - Platinum Derivatives(Cisplatin and Carboplatin)].

作者信息

Matsuoka Ayumu, Ando Yuichi

机构信息

Dept. of Clinical Oncology and Chemotherapy, Nagoya University Hospital.

出版信息

Gan To Kagaku Ryoho. 2017 Mar;44(3):200-203.

Abstract

Cisplatin, a first-generation platinum derivative, is one of the most widely used anticancer agents and can treat a broad spectrum of malignancies. Cisplatin-induced nephrotoxicity is a major dose-limiting side effect resulting from damage to the proximal tubules of the kidney. This nephrotoxicity can be prevented by lowering the concentration of cisplatin and shortening the period of cisplatin exposure to the proximal tubules. In clinical practice, high-volume hydration(>3 L intravenous isotonic saline), forced diuresis(mannitol and/or furosemide), and magnesium supplementation have been generally used to lower the risk of cisplatin-induced nephrotoxicity. Short hydration(short-term, low-volume hydration with oral fluid intake)has recently been undertaken among patients with reserved renal function and good performance status, especially in outpatient settings. Carboplatin is a second-generation platinum-based agent that is almost completely excreted from the kidneys following its administration. Its pharmacokinetics can be predicted based on the glomerular filtration rate(GFR). The area under the blood concentration-time curve(AUC), an indicator of drug exposure volume in the body, is closely correlated with hematotoxicity and antitumor effect. It is now a widespread practice to set carboplatin doses based on the GFR after establishing a target AUC. This article describes the characteristics of these 2 platinum-based drugs, focusing on the recommendations based on the recently published guidelines regarding nephropathy in patients undergoing cancer drug therapy.

摘要

顺铂是第一代铂类衍生物,是应用最广泛的抗癌药物之一,可治疗多种恶性肿瘤。顺铂诱导的肾毒性是一种主要的剂量限制性副作用,由肾脏近端小管受损所致。通过降低顺铂浓度和缩短顺铂与近端小管的接触时间,可以预防这种肾毒性。在临床实践中,通常采用大量补液(静脉输注>3L等渗盐水)、强制利尿(甘露醇和/或呋塞米)以及补充镁来降低顺铂诱导的肾毒性风险。对于肾功能储备良好且身体状况良好的患者,尤其是在门诊环境中,最近已开始采用短程补液(短期、少量口服补液)。卡铂是第二代铂类药物,给药后几乎完全经肾脏排泄。其药代动力学可根据肾小球滤过率(GFR)进行预测。血药浓度-时间曲线下面积(AUC)是体内药物暴露量的指标,与血液毒性和抗肿瘤效果密切相关。目前的普遍做法是在确定目标AUC后,根据GFR来设定卡铂剂量。本文描述了这两种铂类药物的特点,重点介绍了基于最近发布的癌症药物治疗患者肾病指南的建议。

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