van Warmerdam L J, Rodenhuis S, ten Bokkel Huinink W W, Maes R A, Beijnen J H
Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam.
J Cancer Res Clin Oncol. 1995;121(8):478-86. doi: 10.1007/BF01218365.
Carboplatin is a chemotherapeutic agent frequently used in the treatment of various malignancies. The myelotoxicity and clinical efficacy of carboplatin correlate with the clearance of the drug, which is correlated to the glomerular filtration rate (GFR). Dosing of this agent based solely upon the patients body surface area is therefore not accurate enough; the GFR, and thus the clearance of carboplatin differ in each patient irrespective of the body area. Consequently, some patients undergo a higher systemic exposure, expressed as the area under the plasma concentration/time curve (AUC), than others when dosages of carboplatin are given on the basis of the body surface area. A high AUC correlates with increased toxicity, thus increasing the risks of the treatment, but in the case of a low AUC the therapeutical efficacy decreases. This indicates that an individual dosing strategy is warranted to obtain the optimal AUC. In this article, the development and application of a simple equation, known as the Calvert formula, are discussed. This formula can be used to calculate the carboplatin dose accurately in order to obtain a target AUC by using only the GFR. The formula is: dose (mg) = AUC (mg ml-1 min) x [GFR (ml/min) + 25 (ml/min)]. This formula has proven to be, in both retrospective and prospective studies, a reliable tool to calculate the optimal dose of carboplatin Future studies should determine the value of the creatinine clearance as a measure for the GFR.
卡铂是一种常用于治疗各种恶性肿瘤的化疗药物。卡铂的骨髓毒性和临床疗效与药物清除率相关,而药物清除率又与肾小球滤过率(GFR)相关。因此,仅根据患者的体表面积来确定该药物的剂量是不够准确的;无论体表面积如何,每个患者的GFR以及卡铂的清除率都有所不同。因此,当根据体表面积给予卡铂剂量时,一些患者的全身暴露量(以血浆浓度/时间曲线下面积(AUC)表示)高于其他患者。高AUC与毒性增加相关,从而增加了治疗风险,但在AUC较低的情况下,治疗效果会降低。这表明需要一种个体化的给药策略来获得最佳的AUC。在本文中,将讨论一种简单公式(称为卡尔弗特公式)的开发和应用。该公式可仅通过使用GFR来准确计算卡铂剂量,以获得目标AUC。公式为:剂量(mg)=AUC(mg·ml⁻¹·min)×[GFR(ml/min)+25(ml/min)]。在回顾性和前瞻性研究中,该公式已被证明是计算卡铂最佳剂量的可靠工具。未来的研究应确定肌酐清除率作为GFR测量指标的价值。