Donahue A, McCune J S, Faucette S, Gillenwater H H, Kowalski R J, Socinski M A, Lindley C
University of North Carolina, University of Washington, CB #7360, Beard Hall, Box 357630, Chapel Hill, NC 27599-7360 Seattle, WA 98195, USA.
Cancer Chemother Pharmacol. 2001 May;47(5):373-9. doi: 10.1007/s002800000260.
Carboplatin is frequently dosed to achieve a desired area under the plasma concentration-time curve (AUC) by using the Calvert or Chatelut equations to estimate carboplatin clearance. Accurate determination of glomerular filtration rate (GFR) is necessary to correctly calculate carboplatin clearance using the Calvert equation. In clinical practice, the Cockcroft-Gault formula is frequently used to estimate GFR, but this practice has been reported to under- and overestimate carboplatin clearance. The purpose of this trial was to compare determinations of carboplatin clearance using the Chatelut equation and four separate GFR determinations, including 99mTc-DTPA, the Cockcroft-Gault formula, a 24-h urine collection and a 2-h urine collection.
Carboplatin clearance was estimated in 21 previously untreated extensive-stage small-cell lung cancer patients. GFR was determined using 99mTc-DTPA, the Cockcroft-Gault formula, 24-h urine collection and 2-h urine collection. Serum and urine creatinine concentrations were measured using enzymatic assays. The carboplatin clearance was then calculated by individually adding 25 to the four GFR determinations based on the Calvert equation, which states that carboplatin clearance equals GFR + 25 (nonrenal clearance). The carboplatin clearance was also estimated using the Chatelut equation. The five determinations of carboplatin clearance were compared using Friedman's test and post-hoc Wilcoxon signed rank tests. Precision and bias for each carboplatin clearance determination were calculated assuming that 99mTc-DTPA provided the most accurate measure of GFR.
A statistically significant difference was found between the five methods of estimating carboplatin clearance (P < 0.001). No difference was found between carboplatin clearance calculated using 99mTc-DTPA and the Chatelut equation, the Cockcroft-Gault formula or the 2-h urine collection. The Chatelut equation provided more precision and less bias than the 2-h urine collection (median precision 20% and 30%, median bias -1% and -18%, respectively).
Compared to 99mTc-DTPA, the Chatelut equation more accurately estimates carboplatin clearance than the Cockcroft-Gault formula, the 2-h urine collection and the 24-h urine collection. The greater negative bias found for the latter three estimates of carboplatin clearance could result in underdosing of carboplatin.
卡铂给药常通过使用卡尔弗特（Calvert）或沙泰吕（Chatelut）方程来估计卡铂清除率，以达到血浆浓度 - 时间曲线下面积（AUC）的目标值。准确测定肾小球滤过率（GFR）对于使用卡尔弗特方程正确计算卡铂清除率是必要的。在临床实践中，常用考克饶夫 - 高尔特（Cockcroft - Gault）公式来估计GFR，但据报道这种做法会低估或高估卡铂清除率。本试验的目的是比较使用沙泰吕方程和四种不同的GFR测定方法（包括99mTc - DTPA、考克饶夫 - 高尔特公式、24小时尿液收集和2小时尿液收集）来测定卡铂清除率。
对21例先前未接受治疗的广泛期小细胞肺癌患者进行卡铂清除率估计。使用99mTc - DTPA、考克饶夫 - 高尔特公式、24小时尿液收集和2小时尿液收集来测定GFR。采用酶法测定血清和尿液肌酐浓度。然后根据卡尔弗特方程，通过分别在四种GFR测定值上加上25来计算卡铂清除率，该方程表明卡铂清除率等于GFR + 25（非肾清除率）。也使用沙泰吕方程估计卡铂清除率。使用弗里德曼（Friedman）检验和事后威尔科克森符号秩检验比较卡铂清除率的五种测定结果。假设99mTc - DTPA提供了最准确的GFR测量值，计算每种卡铂清除率测定的精密度和偏差。
在估计卡铂清除率的五种方法之间发现了统计学上的显著差异（P < 0.001）。使用99mTc - DTPA、沙泰吕方程、考克饶夫 - 高尔特公式或2小时尿液收集计算的卡铂清除率之间未发现差异。与2小时尿液收集相比，沙泰吕方程提供了更高的精密度和更低的偏差（中位精密度分别为20%和30%，中位偏差分别为 - 1%和 - 18%）。
与99mTc - DTPA相比，沙泰吕方程比考克饶夫 - 高尔特公式、2小时尿液收集和24小时尿液收集更准确地估计卡铂清除率。后三种卡铂清除率估计值中发现的更大的负偏差可能导致卡铂给药不足。
