Department of Pediatrics, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Drugs R D. 2017 Sep;17(3):469-474. doi: 10.1007/s40268-017-0190-z.
Bevacizumab is a recombinant antibody that is increasingly used in pediatric malignancies. The pharmacokinetics of bevacizumab in pediatric patients have been shown to be influenced by tumor localization and body weight. In this report, we present data on the pharmacokinetics and safety of bevacizumab in children under the age of 3 years with central nervous system (CNS) malignancies.
Three patients (mean age 22 months) were treated with intravenous bevacizumab 10 mg/kg every 2 weeks. In total, 20 trough and peak bevacizumab concentrations of 10 treatment cycles were obtained at steady state.
Bevacizumab was generally well-tolerated in this age group. The mean trough concentration was 127 ± 29 µg/ml (range 77-155), and the mean peak concentration was 149 ± 13 µg/ml (range 113-157). Trough and peak levels were stable upon repeated treatment cycles in the same patient. In contrast, we determined strong interindividual variations in trough levels. Whereas the plasma concentration of the oldest patient matched the prediction of a previously published model, younger patients showed markedly higher trough levels.
Serum peak concentrations of bevacizumab in children under the age of 3 years with CNS malignancies are in a similar magnitude to that found in older children and adults. Thus, a dosing schedule of bevacizumab 10 mg/kg every 2 weeks can be considered sufficient and safe, even in very young children. We further show that very young children with CNS malignancies show a markedly reduced plasma clearance, possibly related to lower body weight or differences in clearance mechanisms of antibodies.
贝伐单抗是一种重组抗体，越来越多地用于儿科恶性肿瘤。贝伐单抗在儿科患者中的药代动力学已被证明受肿瘤定位和体重的影响。在本报告中，我们介绍了年龄在 3 岁以下患有中枢神经系统（CNS）恶性肿瘤的儿童使用贝伐单抗的药代动力学和安全性数据。
3 名患者（平均年龄 22 个月）接受每 2 周静脉注射 10mg/kg 的贝伐单抗治疗。在稳态下，总共获得了 10 个治疗周期的 20 个贝伐单抗谷浓度和峰浓度。
在该年龄组中，贝伐单抗通常具有良好的耐受性。平均谷浓度为 127±29μg/ml（范围 77-155），平均峰浓度为 149±13μg/ml（范围 113-157）。在同一患者的重复治疗周期中，谷浓度和峰浓度稳定。相比之下，我们确定了谷浓度的个体间存在很强的差异。虽然最年长患者的血浆浓度与之前发表的模型预测相符，但年龄较小的患者显示出明显更高的谷浓度。
患有 CNS 恶性肿瘤的 3 岁以下儿童的贝伐单抗血清峰浓度与年龄较大的儿童和成人相似。因此，每 2 周 10mg/kg 的贝伐单抗剂量方案可以被认为是足够和安全的，即使是在非常年幼的儿童中。我们进一步表明，患有 CNS 恶性肿瘤的非常年幼的儿童显示出明显降低的血浆清除率，这可能与体重较低或抗体清除机制的差异有关。
