Pharmacokinetics and safety of pegylated recombinant human granulocyte colony‐stimulating factor in children with acute leukaemia.

Aims: This open‐label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony‐stimulating factor (PEG‐rhG‐CSF) for the treatment of chemotherapy‐induced neutropenia in children with acute leukaemia. Methods: PEG‐rhG‐CSF was administered as a single 100 mcg/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG‐rhG‐CSF. PEG‐rhG‐CSF serum concentrations were determined by an enzyme‐linked immunosorbent assay. Population pharmacokinetic (PPK) analysis was implemented using the nonlinear mixed‐effects model. Short‐term safety was evaluated through adverse events collection (registered at clinicaltrials.gov identifier: 03844360). Results: A total of 16 acute leukaemia patients (1.8–13.6 years) were included, of whom two (12.5%) had grade 3 neutropenia, six (37.5%) had grade 4 neutropenia, and eight (50.0%) had severe neutropenia. For PPK modelling, 64 PEG‐rhG‐CSF serum concentrations were obtainable. A one‐compartment model with first‐order elimination was used for pharmacokinetic data modelling. The current weight was a significant covariate. The median (range) of clearance (CL) and area under the serum concentration–time curve (AUC) were 5.65 (1.49–14.45) mL/h/kg and 16514.75 (6632.45–54423.30) ng·h/mL, respectively. Bone pain, pyrexia, anaphylaxis and nephrotoxicity were not observed. One patient died 13 days after administration, and the objective assessment of causality was that an association with PEG‐rhG‐CSF was "possible". Conclusions: The AUC of PEG‐rhG‐CSF (100 mcg/kg, 3 mg maximum dose) in paediatric patients with acute leukaemia were similar to those of PEG‐rhG‐CSF (100 mcg/kg) in children with sarcoma. PEG‐rhG‐CSF is safe, representing an important therapeutic option for chemotherapy‐induced neutropenia in paediatric patients with acute leukaemia. [ABSTRACT FROM AUTHOR]