Pegylated recombinant human granulocyte colony stimulating factor (Jiuyuan Gene)

NCCN guidelines recommend a dose of 100 μg/kg or a fixed dose of 6 mg pegylated recombinant human granulocyte colony‐stimulating factor (PEG rhG‐CSF) for chemotherapy‐induced neutropenia. However, a single dose of 60 μg/kg or 100 μg/kg produced a similar neutrophil response among patients with chemotherapy‐induced neutropenia (CIN). Thus, this prospective randomized study was designed to investigate the efficacy of 3 mg PEG rhG‐CSF in preventing acute lower respiratory tract infection (ALRTI) after chemotherapy.

Patients with stage IIIB/IVA lung cancer who underwent chemotherapy were randomly divided into a (i) control group, and (ii) treatment group subject to 3 mg PEG rhG‐CSF after chemotherapy. Patients in the control group were administered rhG‐CSF (5 μg/kg) when decreased absolute neutrophil count (ANC) reached grade 3 of adverse events. The primary outcome was incidence of ALRTI, and the secondary outcomes included ANC, febrile neutropenia (FN), incidence of delayed chemotherapy, infection‐related medical expenses and adverse reactions.

Compared with the control group, there was a significant decrease in the incidence of ALRTI (9.6% vs. 24.6%, p < 0.01), FN (1.7% vs. 7.3%, p < 0.001) and neutropenia (8.3% vs. 23.3%, p < 0.01) in the PEG‐rhG‐CSF group. The incidence of ALRTI was significantly correlated with the grade of CTCAE on ANC. The main adverse reactions of PEG‐rhG‐CSF were pain and fatigue, among which three cases showed pain of ≥ grade 3. The cost of infection‐associated medical expenditure in the treatment group was greatly reduced compared with the control group (p < 0.001).

ALRTI could well be prevented after prophylactic application of PEG‐rhG‐CSF (3 mg), and was related to the reduced neutropenia.

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.

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).

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”.

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.