Optimizing drug regimens in cancer chemotherapy: a simulation study using a PK-PD model

被引:64
作者
Barbolosi, D [1 ]
Iliadis, A [1 ]
机构
[1] Fac Pharm Marseille, UPRES EA 3286, F-13385 Marseille 5, France
关键词
high-dose chemotherapy; mathematical modeling; optimal control; tumor reduction; white blood cell toxicity; dynamical AUC; pharmacokinetics; pharmacodynamics;
D O I
10.1016/S0010-4825(00)00032-9
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
In cancer chemotherapy, it is important to design treatment strategies for drug protocols that ensure a desired rate of tumor cell kill without overdosing the host. Mathematical modeling was used for optimization in which we minimize the end value of the tumor cells while limiting toxicity by always maintaining the white blood cell count beyond a limit. The optimal solution for this is a mixture of an initial bolus application of drug followed by no drug and then continuous infusion that keeps the normal cell population at its lower limit while decreasing the tumor cell population. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:157 / 172
页数:16
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