Panday V R, van Warmerdam L J, Huizing M T, Rodenhuis S, Schellens J H, Beijnen J H
Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam.
Cancer Chemother Pharmacol. 1999;43(5):435-8. doi: 10.1007/s002800050919.
It has been observed that the area under the free carboplatin concentration in plasma ultrafiltrate versus time curve (AUC) is related to toxicity and tumour response. For this reason, it can be important to measure the carboplatin AUC and subsequently adjust the dose to achieve a predefined target AUC. The use of limited sampling strategies enables relatively simple measurement and calculation of actual carboplatin AUCs.
We studied the performance of a limited sampling model, based on a single 24-h sample (the Ghazal-Aswad model). in 52 patients who received carboplatin in two different chemotherapy regimens (a carboplatin-paclitaxel combination and a high-dose carboplatin-thiotepa-cyclophosphamide combination).
The measured mean AUC in our population was 4.1 min x mg/ml (median 3.9, range 1.9 6.3, SD 1.0 min x mg/ml). With the limited sampling model, the predicted mean AUC was 4.4 min x mg/ml (median 4.2, range 2.4-8.4, SD 1.2 min x mg/ml). Statistical analysis revealed that the model was slightly biased (MPE%, 6.5%), but imprecise (RMSE%, 20.6%) in our study population.
Although easy and attractive to use, the Ghazal-Aswad formula is not precise enough to predict the carboplatin AUC, and needs to be evaluated prospectively in other patient populations.
据观察,血浆超滤液中游离卡铂浓度随时间变化曲线下面积(AUC)与毒性和肿瘤反应相关。因此,测量卡铂AUC并随后调整剂量以达到预定的目标AUC可能很重要。使用有限采样策略能够相对简单地测量和计算实际的卡铂AUC。
我们研究了基于单个24小时样本的有限采样模型(加扎尔-阿斯瓦德模型)的性能。研究对象为52例接受两种不同化疗方案(卡铂-紫杉醇联合方案和高剂量卡铂-噻替派-环磷酰胺联合方案)的患者。
我们研究人群中测得的平均AUC为4.1分钟×毫克/毫升(中位数3.9,范围1.9 - 6.3,标准差1.0分钟×毫克/毫升)。使用有限采样模型,预测的平均AUC为4.4分钟×毫克/毫升(中位数4.2,范围2.4 - 8.4,标准差1.2分钟×毫克/毫升)。统计分析表明,在我们的研究人群中,该模型存在轻微偏差(平均百分比误差,6.5%),但不够精确(均方根误差百分比,20.6%)。
尽管加扎尔-阿斯瓦德公式使用起来简便且有吸引力,但它不够精确,无法预测卡铂AUC,需要在其他患者人群中进行前瞻性评估。