Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada.
Cancer Chemother Pharmacol. 2011 Jan;67(1):93-101. doi: 10.1007/s00280-010-1288-y. Epub 2010 Mar 5.
Although body composition has emerged as an important predictor of drug efficacy and toxicity, explanations for this association are unclear. Our goal was to investigate relationships between lean body mass (LBM), liver size/function and epirubicin pharmacokinetics (PK) and toxicity.
Data from a clinical study (n = 24) of patients with breast cancer receiving adjuvant intravenous FE(100)C chemotherapy were used to examine relationships between LBM, liver size, and epirubicin clearance. Muscle tissue and liver mass were measured by analysis of computerized tomography cross-sectional images, and an extrapolation of muscle mass to total LBM compartment was employed. Population PK analysis of epirubicin was undertaken to test effects of body composition on epirubicin clearance and area under the curve (AUC).
Estimated LBM was extremely variable in this cohort ranging from 32.9 to 67.3 kg. LBM was associated with neutrophil nadir (r = 0.5, P = 0.023), and mean LBM was lower for patients presenting with toxicity compared to those where toxicity was absent (41.6 vs. 56.2 kg, P = 0.002); 33% of variance in clearance was explained by LBM and aspartate aminotransferase (AST). Liver mass was not related to epirubicin clearance likely due to larger livers presenting with larger fat content, but liver attenuation (degree of fat infiltration) and AST were associated with AUC.
To our knowledge, this is the first study to examine relationships between LBM, liver mass/function and epirubicin PK and toxicity. This exploratory work investigates the notion of organs and tissues having distinctive contributions to the distribution and metabolism of antineoplastic drugs.
尽管身体成分已成为预测药物疗效和毒性的重要指标，但对于这种关联的解释尚不清楚。我们的目标是研究瘦体重（LBM）、肝脏大小/功能与表柔比星药代动力学（PK）和毒性之间的关系。
使用来自接受辅助静脉注射 FE（100）C 化疗的乳腺癌患者的临床研究（n=24）的数据，研究 LBM、肝脏大小与表柔比星清除率之间的关系。通过对计算机断层扫描横断图像的分析来测量肌肉组织和肝脏质量，并将肌肉质量外推到总 LBM 隔室。进行表柔比星群体 PK 分析，以检验身体成分对表柔比星清除率和曲线下面积（AUC）的影响。
该队列中估计的 LBM 变化非常大，范围为 32.9 至 67.3kg。LBM 与中性粒细胞最低点相关（r=0.5，P=0.023），并且出现毒性的患者的平均 LBM 低于无毒性的患者（41.6 与 56.2kg，P=0.002）；清除率的 33%可由 LBM 和天冬氨酸转氨酶（AST）解释。由于较大的肝脏表现出较大的脂肪含量，因此肝脏质量与表柔比星清除率无关，但肝脏衰减（脂肪浸润程度）和 AST 与 AUC 相关。
据我们所知，这是第一项研究 LBM、肝脏质量/功能与表柔比星 PK 和毒性之间关系的研究。这项探索性工作研究了器官和组织对抗肿瘤药物分布和代谢的独特贡献的概念。
