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.
PURPOSE:Granulocyte colony-stimulating factor (G-CSF) is often used in cancerpatients 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.
Authors: Markus Scholz; Sibylle Schirm; Marcus Wetzler; Christoph Engel; Markus Loeffler Journal: Theor Biol Med Model Date: 2012-07-30 Impact factor: 2.432
Authors: Wojciech Krzyzanski; John M Harrold; Liviawati S Wu; Juan Jose Perez-Ruixo Journal: J Pharmacokinet Pharmacodyn Date: 2016-09-09 Impact factor: 2.745
Authors: Murad Melhem; Isabelle Delor; Juan Jose Pérez-Ruixo; John Harrold; Andrew Chow; Liviawati Wu; Philippe Jacqmin Journal: Br J Clin Pharmacol Date: 2018-02-20 Impact factor: 4.335