Pharmacokinetics of Bevacizumab in Three Patients Under the Age of 3 Years with CNS Malignancies

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.