Flat-fixed dosing versus body surface area-based dosing of anticancer drugs in adults: Does it make a difference?
Flat-fixed dosing versus body surface area-based dosing of anticancer drugs in adults: Does it make a difference?
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DOI：
10.1634/theoncologist.12-8-913
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发表时间：
2007-01-01
期刊：
影响因子：
5.8
通讯作者：
Sparreboom, Alex
中科院分区：
文献类型：
--
作者：
Mathijssen, Ron H. J.;De Jong, Floris A.;Sparreboom, Alex
目前使用体表面积（BSA）给药抗癌药物的做法是在临床肿瘤学实施了半个世纪前。通过校正BSA，通常假设癌症患者将接受与可接受的毒性程度相关的特定细胞毒性药物的剂量，而不降低药剂的治疗效果。最近，怀疑出现了这种假设，并为许多药物，BSA对这些药物的药代动力学的影响，因此进行了回顾性研究。在（到目前为止）大多数情况下，使用BSA不会减少成人药代动力学的个体间差异，因此，缺乏在成人给药中进一步使用该工具的逻辑依据。因此，已经提出了替代给药策略以取代基于BSA的给药。已建议采用固定剂量给药方案，从而避免潜在的剂量计算错误。由于固定剂量给药通常不会导致更大的药代动力学变异性，因此似乎并不比使用基于BSA的给药更差。虽然它提供了一种简化，但可以质疑是否将其称为改进。实施所谓的基因分型和表型策略，以及治疗药物监测，可能更具临床价值。最后，基于BSA的非科学给药策略应该被替代策略所取代。尽管缺乏基本的基础知识，但基于BSA的给药在临床肿瘤学中似乎仍然是“不可触及的”。即使替代品将被证明是无可争议的更好，许多障碍可能必须克服之前，医生将愿意禁止基于BSA的剂量。
The current practice of using body-surface area (BSA) in dosing anticancer agents was implemented in clinical oncology half a century ago. By correcting for BSA, it was generally assumed that cancer patients would receive a dose of a particular cytotoxic drug associated with an acceptable degree of toxicities without reducing the agent's therapeutic effect. More recently, doubt has arisen to this hypothesis, and for many drugs, the effects of BSA on the pharmacokinetics of these agents have therefore been studied retrospectively. In (by far) most cases, use of BSA does not reduce the interindividual variation in the pharmacokinetics of adults, and thus, a logical rationale for further use of this tool in dosing adults is lacking. As a result, alternative dosing strategies have been proposed in order to replace BSA-based dosing. Flat-fixed dosing regimens have been suggested, thereby avoiding potential dose calculation mistakes. As flat-fixed dosing does not typically lead to greater pharmacokinetic variability, it does not seem worse than using BSA-based dosing. While it provides a simplification, it can, however, be questioned whether to call this an improvement or not. The implementation of socalled genotyping and phenotyping strategies, and therapeutic drug monitoring, may probably be of more clinical value. In the end, the nonscientifically based BSA-based dosing strategy should be replaced by alternative strategies. Despite the lack of basic fundamentals, BSA-based dosing still seems "untouchable" in clinical oncology. Even when alternatives will be shown to be indisputably better, many hurdles will probably have to be overcome before physicians will be willing to ban BSA-based dosing.