Role of body surface area in dosing of investigational anticancer agents in adults, 1991-2001
Role of body surface area in dosing of investigational anticancer agents in adults, 1991-2001
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DOI：
10.1093/jnci/94.24.1883
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发表时间：
2002-12-18
影响因子：
10.3
通讯作者：
Sparreboom, A
中科院分区：
文献类型：
--
作者：
Baker, SD;Verweij, J;Sparreboom, A
抗癌药物的处方剂量通常是使用体表面积作为唯一的自变量来计算的，而且已经表明，这种方法仍然会导致患者之间在药物暴露方面存在很大的变异性。在这里，我们回顾评估了从1991年到2001年在I期试验中测试的33种研究药物的药代动力学，作为1650名成年癌症患者的体表面积的函数。其中12种药物是口服给药，19种是静脉给药，两种途径都有。在统计上，33种药物中只有5种药物的患者间药物清除量的可变性降低与基于体表面积的剂量显著相关：二十二碳六烯酸(DHA)-紫杉醇、5-氟尿嘧啶/依利尿嘧啶、紫杉醇、替莫唑胺和曲沙他滨。这些结果不支持在剂量计算中使用体表面积，并建议应评估替代剂量策略。我们的结论是，在未来的I期研究中，不应使用体表面积来确定研究药物的起始剂量。
The prescribed dose of anticancer agents is most commonly calculated using body surface area as the only independent variable, and it has been shown that this approach still results in large interpatient variability in drug exposure. Here, we retrospectively assessed the pharmacokinetics of 33 investigational agents tested in phase I trials from 1991 through 2001, as a function of body surface area in 1650 adult cancer patients. Twelve of the drugs were administered orally, 19 were administered intravenously, and two were administered by both routes. Body surface area-based dosing was statistically significantly associated with a reduction in interpatient variability in drug clearance for only five of the 33 agents: docosahexaenoic acid (DHA)-paclitaxel, 5-fluorouracil/eniluracil, paclitaxel, temozolomide, and troxacitabine. These results do not support the use of body surface area in dose calculations and suggest that alternate dosing strategies should be evaluated. We conclude that body surface area should not be used to determine starting doses of investigational agents in future phase I studies.