Desoize B
GIBSA, laboratoire de pharmacologie, Institut J Godinot, Reims, France.
Bull Cancer. 1993 May;80(5):376-90.
The dose of anticancer drugs is currently adjusted to the body surface area of the patient, although for a given body surface, patients have different distribution and metabolism for a given drug. The dose adjustment to the tumour drug content was studied, we noted that it is not always possible to obtain a tumour sample; the sample and its drug content may not be representative of the whole tumour content, this measured drug content is neither indicative for the evaluation of the dose to be administered, nor indicative of the chemotherapy efficacy. The best criterion for the dose adjustment seems to be the plasma concentration of the drug. Correlations between drug plasma concentration and clinical data are examined. The relationship between plasma concentration and efficacy cannot be excellent, since it depends on the presence of resistant cells and on the blood flow through the tumour. A relationship between plasma concentration and toxicity has been reported with many anticancer drugs. The drug plasma concentration and the area under the curve (AUC) give better correlations than the administered dose with efficacy and toxicity. Different methods of dose adjustment are reported. They use mathematical models which allow to decrease the number of blood samples, without losing precision in the pharmacokinetic parameter evaluation. In conclusion, the dose adjustment to the drug plasma concentration or to the AUC can play an important role in improving the chemotherapy efficacy, while toxicity is reduced.
目前，抗癌药物的剂量是根据患者的体表面积来调整的，尽管对于给定的体表面积，患者对给定药物的分布和代谢存在差异。我们研究了根据肿瘤药物含量进行剂量调整的情况，发现并非总能获取肿瘤样本；所取样本及其药物含量可能无法代表整个肿瘤的含量，这种测得的药物含量既不能用于评估给药剂量，也不能表明化疗疗效。剂量调整的最佳标准似乎是药物的血浆浓度。我们研究了药物血浆浓度与临床数据之间的相关性。血浆浓度与疗效之间的关系不可能非常理想，因为这取决于耐药细胞的存在以及通过肿瘤的血流量。许多抗癌药物都报道了血浆浓度与毒性之间的关系。与给药剂量相比，药物血浆浓度和曲线下面积（AUC）与疗效和毒性的相关性更好。本文报道了不同的剂量调整方法。这些方法使用数学模型，在不损失药代动力学参数评估精度的情况下，能够减少血样采集次数。总之，根据药物血浆浓度或AUC进行剂量调整，在提高化疗疗效的同时降低毒性方面可能发挥重要作用。
