Ekhart Corine, de Jonge Milly E, Huitema Alwin D R, Schellens Jan H M, Rodenhuis Sjoerd, Beijnen Jos H
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, and Faculty of Pharmaceutical Sciences, Utrecht University, the Netherlands.
Clin Cancer Res. 2006 Nov 1;12(21):6502-8. doi: 10.1158/1078-0432.CCR-05-1076.
The Calvert formula is a widely applied algorithm for the a priori dosing of carboplatin based on patients glomerular filtration rate (GFR) as accurately measured using the 51Cr-EDTA clearance. Substitution of the GFR in this formula by an estimate of creatinine clearance or GFR as calculated by formulae using serum creatinine (SCR; Cockcroft-Gault, Jelliffe, and Wright) is, however, routine clinical practice in many hospitals. The goal of this study was to validate this practice retrospectively in a large heterogeneous adult patient population.
Concentration-time data of ultrafilterable platinum of 178 patients (280 courses, 3,119 samples) with different types of cancer receiving carboplatin-based chemotherapy in conventional and high doses were available. Data were described with a linear two-compartment population pharmacokinetic model. Relations between SCR-based formulae for estimating renal function and carboplatin clearance were investigated.
None of the tested SCR-based estimates of renal function were relevantly related to the pharmacokinetic variables of carboplatin. Neither SCR (median, 51; range, 18-124 micromol/L) nor the estimated GFR using the three different formulae was related to carboplatin clearance.
Our data do not support the application of modifications of the Calvert formula by estimating GFR from SCR in the a priori dosing of carboplatin in patients with relatively normal renal function (creatinine clearance, >50 mL/min). For targeted carboplatin exposures, the original Calvert formula, measuring GFR using the 51Cr-EDTA clearance, remains the method of choice. Alternatively, in patients with normal renal function, a flat dose based on the mean population carboplatin clearance should be administered.
卡尔弗特公式是一种广泛应用的算法，用于根据患者的肾小球滤过率（GFR）对卡铂进行预先给药，GFR通过51Cr - 乙二胺四乙酸清除率精确测量。然而，在许多医院的常规临床实践中，使用血清肌酐（SCR；Cockcroft - Gault、Jelliffe和Wright公式）计算的肌酐清除率或GFR估计值来替代该公式中的GFR。本研究的目的是在大量异质性成年患者群体中对这种做法进行回顾性验证。
可获得178例不同类型癌症患者（280个疗程，3119份样本）接受常规和高剂量卡铂化疗时的超滤铂浓度 - 时间数据。用线性二室群体药代动力学模型描述数据。研究了基于SCR的肾功能估计公式与卡铂清除率之间的关系。
所测试的基于SCR的肾功能估计值均与卡铂的药代动力学变量无显著相关性。SCR（中位数，51；范围，18 - 124 μmol/L）以及使用三种不同公式估计的GFR均与卡铂清除率无关。
我们的数据不支持在肾功能相对正常（肌酐清除率>50 mL/min）的患者中，通过从SCR估计GFR来修改卡尔弗特公式用于卡铂的预先给药。对于靶向卡铂暴露，使用51Cr - 乙二胺四乙酸清除率测量GFR的原始卡尔弗特公式仍然是首选方法。或者，对于肾功能正常的患者，应根据群体平均卡铂清除率给予固定剂量。
