Model-based approach to describe G-CSF effects in carboplatin-treated cancer patients

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.