Felici A, Verweij J, Sparreboom A
Department of Medical Oncology, Erasmus MC-Daniel den Hoed, 3075 EA Rotterdam, The Netherlands.
Eur J Cancer. 2002 Sep;38(13):1677-84. doi: 10.1016/s0959-8049(02)00151-x.
Most anticancer drugs are characterised by a narrow therapeutic window; hence, a small change in dose can lead to poor antitumour effects or an unacceptable degree of toxicity. The rationale for using body surface area (BSA) to dose antineoplastic agents is to normalise the effects of drugs, and accordingly, it has been routinely employed as the only independent variable. In the last 10 years, however, several studies have shown a poor relationship of BSA for predicting drug exposure, and an irrelevant correlation between this variable and pharmacokinetic (PK) parameters. In this paper, the results of this relationship for various commonly used antineoplastic agents are reviewed, and the influence of BSA to decrease the total variability in clearance among patients is underlined. As reported, BSA failed to individualise the effects of the majority of the agents explored. The criteria that can predict a clinically meaningful relationship between BSA and drug clearance are discussed, and some alternative strategies to dose agents when BSA has proven to be useless are proposed.
大多数抗癌药物的特点是治疗窗狭窄;因此,剂量的微小变化可能导致抗肿瘤效果不佳或出现不可接受程度的毒性。使用体表面积(BSA)来确定抗肿瘤药物剂量的基本原理是使药物效果标准化,因此,它一直被常规用作唯一的自变量。然而,在过去10年中,多项研究表明,BSA在预测药物暴露方面关系不佳,且该变量与药代动力学(PK)参数之间的相关性不大。本文回顾了各种常用抗肿瘤药物的这种关系的结果,并强调了BSA对降低患者间清除率总变异性的影响。如所报道的,BSA未能使所研究的大多数药物的效果个体化。讨论了能够预测BSA与药物清除率之间具有临床意义关系的标准,并提出了在BSA已被证明无用时确定药物剂量的一些替代策略。