Pharmacokinetics of oral vinorelbine in French children with recurrent or progressive primary low-grade glioma

Aims: There is a crucial need for pharmacokinetic (PK) data on oral vinorelbine (VNR) in the paediatric population. The aim of this work was to assess the PK profile of orally administered VNR in children with recurrent/progressive primary low-grade glioma (LGG). Methods: A multicentre, open-label, single-arm intervention phase II study was conducted. Patients, aged between 6 and 18 years, with histologically confirmed recurrent or progressive primary LGG or non-documented typical optic pathway tumours, were included. PK parameters were estimated by non-compartmental analysis using Phoenix WinNonlin® software (version 8.0, Certara, Inc.). The influence of demographic and biological covariates on VNR PK parameters was investigated using a multivariate linear regression analysis. Results: PK analysis included 36 patients with a median age (range) of 11 (6–17) years. Estimates of apparent oral clearance (CL/F), apparent volume of distribution (V/F), half-life (t_1/2) and their between-subject variability (CV%) at 60 mg m⁻² dose level, were 472 L h⁻¹ (51.8%), 7002 L (57.9%) and 10 h (21.0%), respectively. Negligible accumulation of VNR between C1 and C2 was observed. CL/F and V/F were found to increase with body surface area (BSA) (P =.004). Lower area under the concentration–time curve (AUC) levels were observed among children in comparison to adults. Conclusion: Higher doses may be necessary for children with LGG. BSA showed a significant impact on VNR systemic exposure. We believe that our findings will serve as a basis for further studies to better characterize the concentration–response relationships of VNR among paediatric patients.