Kintzel P E, Dorr R T
Department of Pharmacy Practice, University of Arizona Health Sciences Center, Tucson 85724.
Cancer Treat Rev. 1995 Jan;21(1):33-64. doi: 10.1016/0305-7372(95)90010-1.
The narrow therapeutic index of anticancer drugs presents a clinical dilemma when these agents are administered to patients with impaired or unstable renal function. The purpose of this review is to (i) describe the nephrotoxicity of certain anticancer drugs, (ii) evaluate the fraction of renal clearance for pertinent anticancer drugs, and (iii) make general recommendations for the dosing of these drugs in the presence of impaired renal function. Pharmacokinetic, pharmacodynamic, and clinical toxicity information was obtained from current scientific and clinical literature. Recommendations for dosage adjustment of drugs is based on their nephrotoxicity, or renal clearance equal to or exceeding 30% of the administered dose. The specific formula used to calculate dosage adjustment of renally cleared anticancer drugs is based on fundamental pharmacokinetic principles. In addition, prospectively validated formulae for the dosage adjustment of specific agents, such as carboplatin are also reviewed. Forty-eight anticancer drugs are reviewed in this report. Nephrotoxicity is associated with 12 of these agents (Table 1). Renal clearance equal to or exceeding 30% of the administered dose is a characteristic of 17 of the drugs studied (Table 2), and a general recommendation for dose adjustment of these anticancer drugs is presented in Table 3. Renal clearance that is less than 30% of the administered dose is a feature of 31 anticancer drugs (Table 4) included in this review. This report provides general guidelines to adjust doses of renally excreted or nephrotoxic anticancer drugs in patients who present with altered renal function.
当给肾功能受损或不稳定的患者使用抗癌药物时，这些药物狭窄的治疗指数带来了临床难题。本综述的目的是：（i）描述某些抗癌药物的肾毒性；（ii）评估相关抗癌药物的肾清除率；（iii）针对肾功能受损患者使用这些药物的剂量给出一般性建议。药代动力学、药效学和临床毒性信息来自当前的科学和临床文献。药物剂量调整建议基于其肾毒性，或肾清除率等于或超过给药剂量的30%。用于计算经肾清除的抗癌药物剂量调整的具体公式基于基本的药代动力学原理。此外，还综述了特定药物（如卡铂）剂量调整的前瞻性验证公式。本报告综述了48种抗癌药物。其中12种药物具有肾毒性（表1）。所研究的17种药物的特征是肾清除率等于或超过给药剂量的30%（表2），表3给出了这些抗癌药物剂量调整的一般性建议。本综述纳入的31种抗癌药物的特征是肾清除率低于给药剂量的30%（表4）。本报告为肾功能改变的患者调整经肾排泄或具有肾毒性的抗癌药物剂量提供了一般性指导原则。
