Gurney H P, Ackland S, Gebski V, Farrell G
Department of Medical Oncology and Palliative Care, Westmead Hospital, Australia.
J Clin Oncol. 1998 Jul;16(7):2299-304. doi: 10.1200/JCO.1998.16.7.2299.
An exploratory study to test whether body-surface area (BSA) should be used for the calculation of epirubicin dose.
The relationship between pretreatment characteristics and the effects of epirubicin were investigated in 20 chemotherapy-naive patients. Measurements of body size, renal and hepatic function, and other factors were correlated with epirubicin pharmacokinetics (PK) and epirubicin-induced neutropenia. All patients received 150 mg of epirubicin infused continuously over 120 hours, regardless of body size. Factors were analyzed by univariate and multivariate linear regression.
There were no correlations between BSA or weight with any PK parameter or with the degree of neutropenia. In multivariate analysis, indicators of liver function were the only factors that correlated with neutropenia and epirubicin PK. Thus, correlations for neutropenia were seen with antipyrine clearance (P = .003), activated partial thromboplastin time (APTT) (P = .005) and serum transferrin (P = .01). Further, the area under the concentration-time curve (AUC) for epirubicin correlated with prothrombin index (P < .01), antipyrine clearance (P < .01), and serum bile salt concentration (P = .03), and there were similar correlations for epirubicin steady-state concentration (CpSS). Epirubicin clearance correlated with antipyrine clearance (P = .02). PK parameters for dihydroepirubicin correlated with prothombin index, serum transferrin, and bile salt concentrations (P < .001 for all correlations). Because of the number of statistical examinations performed, some of these correlations may be spurious. However, some are likely to be real, since the same variables repeatedly correlated with different epirubicin-associated outcomes. There were no correlations between epirubicin PK indices or neutropenia and serum aminotransferase levels or other biochemical liver function tests, creatinine, or any of the clinical factors examined.
These results led us to question the use of BSA for epirubicin dose calculation. In contrast, quantitative liver function tests may give a better indication of drug handling and toxicity and may be useful to determine more accurate methods for dose calculation of epirubicin.
一项探索性研究，旨在测试是否应使用体表面积（BSA）来计算表柔比星剂量。
对20例初治化疗患者的预处理特征与表柔比星疗效之间的关系进行了研究。测量身体大小、肾功能和肝功能以及其他因素，并将其与表柔比星药代动力学（PK）和表柔比星诱导的中性粒细胞减少相关联。所有患者均接受150mg表柔比星，持续120小时静脉输注，无论身体大小如何。通过单变量和多变量线性回归分析各项因素。
BSA或体重与任何PK参数或中性粒细胞减少程度之间均无相关性。在多变量分析中，肝功能指标是与中性粒细胞减少和表柔比星PK相关的唯一因素。因此，观察到中性粒细胞减少与安替比林清除率（P = 0.003）、活化部分凝血活酶时间（APTT）（P = 0.005）和血清转铁蛋白（P = 0.01）相关。此外，表柔比星的浓度-时间曲线下面积（AUC）与凝血酶原指数（P < 0.01）、安替比林清除率（P < 0.01）和血清胆汁盐浓度（P = 0.03）相关，表柔比星稳态浓度（CpSS）也有类似的相关性。表柔比星清除率与安替比林清除率相关（P = 0.02）。表柔比星的PK参数与凝血酶原指数、血清转铁蛋白和胆汁盐浓度相关（所有相关性P < 0.001）。由于进行的统计检验数量较多，其中一些相关性可能是虚假的。然而，有些可能是真实的，因为相同的变量反复与不同的表柔比星相关结局相关。表柔比星PK指标或中性粒细胞减少与血清转氨酶水平或其他生化肝功能检查、肌酐或任何所检查的临床因素之间均无相关性。
这些结果使我们对使用BSA计算表柔比星剂量产生质疑。相比之下，定量肝功能检查可能能更好地反映药物处理和毒性情况，可能有助于确定更准确的表柔比星剂量计算方法。
