CRCT (Cancer Research Centre of Toulouse), Université de Toulouse, Inserm UMR 1037, Université Paul Sabatier, 31059 Toulouse Cedex 9, France.
Pharmacy Department, Alder Hey Children's NHS Foundation Trust, Liverpool L12 2AP, UK.
Eur J Cancer. 2018 Mar;91:56-67. doi: 10.1016/j.ejca.2017.11.029. Epub 2018 Jan 12.
To make systemic anti-cancer therapy (SACT) preparation more practicable, dose-banding approaches are currently being introduced in many clinical centres. The present study aimed to determine the potential impact of using recently developed National Health Service in England (NHSE) dose-banding tables in a paediatric setting.
Using pharmacokinetic parameters obtained from 385 drug administrations in 352 children aged from 1 month to 18 years, treated with five drugs (dactinomycin, busulfan, carboplatin, cyclophosphamide and etoposide), individual exposures (area under the plasma drug concentration versus time curve; AUC) obtained using doses rounded according to the published NHSE tables were calculated and compared with those obtained by standard dose calculation methods.
For all five drugs, the relative variation between the NHSE dose and the recommended dose (RecDose) (standard individually calculated dose) was between -6% and +5% as expected. In terms of AUC, there was no statistically significant difference in precision between exposures obtained by the RecDose and those obtained with dose banding (absolute value of relative difference 15-34%).
Based on pharmacokinetic data for these five drugs, the results generated support the implementation of NHSE dose-banding tables. Indeed, inter-patient variability in drug clearance and exposure far outweighs the impact of relatively small drug dose changes associated with dose banding.
为了使全身抗癌治疗（SACT）准备更具操作性，目前许多临床中心正在引入剂量分组方法。本研究旨在确定在儿科环境中使用最近开发的英国国家医疗服务体系（NHS）剂量分组表的潜在影响。
使用 352 名 1 个月至 18 岁儿童的 385 次药物给药获得的药代动力学参数，用五种药物（放线菌素 D、白消安、卡铂、环磷酰胺和依托泊苷）治疗，根据已发表的 NHS 表进行剂量四舍五入得到的个体暴露量（血浆药物浓度与时间曲线下面积；AUC）进行计算，并与标准剂量计算方法获得的暴露量进行比较。
对于所有五种药物，NHSE 剂量与推荐剂量（RecDose）（标准个体计算剂量）之间的相对变化在预期的-6%至+5%之间。就 AUC 而言，RecDose 和剂量分组获得的暴露量之间的精密度没有统计学差异（相对差异绝对值为 15-34%）。
基于这五种药物的药代动力学数据，结果表明支持实施 NHS 剂量分组表。实际上，药物清除率和暴露量的个体间变异性远远超过与剂量分组相关的相对较小药物剂量变化的影响。
