Model-Based Approach to Describe G-CSF Effects in Carboplatin-Treated Cancer Patients

Granulocyte colony-stimulating factor (G-CSF) is often used in cancer patients receiving cytotoxic drugs to prevent or reduce high grade neutropenia. We propose a pharmacokinetic/pharmacodynamic model to describe myelotoxicity in both G-CSF treated and non-treated patients that shall increase our understanding of G-CSF effects. The model was built from absolute neutrophil counts (ANC) obtained in 375 carboplatin-treated patients, 47 of whom received G-CSF. It includes some prior information on G-CSF taken from the literature. Simulations were performed to understand differences in G-CSF effects and explore the impact of G-CSF formulation. Our model well described the data in all patients. Model simulations showed that G-CSF was not as beneficial as expected in some patients. Furthermore, a longer and stronger effect was observed for the pegylated formulation in comparison with the daily standard formulation even if the latter was given for 11 consecutive days. The proposed model allows a mechanistic interpretation of G-CSF effects on ANC and raises the question of a systematic beneficial effect of G-CSF treatment. Other studies are needed to confirm these findings and help identifying patients for whom G-CSF is beneficial.