Optimization of G-CSF dosing schedule in patients treated with eribulin: a modeling approach.
Adult
Aged
Antineoplastic Agents
/ administration & dosage
Breast Neoplasms
/ drug therapy
Drug Administration Schedule
Female
Furans
/ administration & dosage
Granulocyte Colony-Stimulating Factor
/ administration & dosage
Humans
Ketones
/ administration & dosage
Middle Aged
Models, Biological
Neutropenia
/ chemically induced
Breast cancer
Eribulin
G-CSF
Modeling
Neutropenia
PK/PD
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
08
09
2021
accepted:
28
12
2021
pubmed:
9
1
2022
medline:
17
2
2022
entrez:
8
1
2022
Statut:
ppublish
Résumé
Granulocyte colony-stimulating factors (G-CSF) are commonly given to limit chemotherapy-induced neutropenia, but, in case of weekly chemotherapy such as eribulin, their administration schedules remain empirical. This pharmacokinetic/pharmacodynamic (PK/PD) study was conducted to establish the effect of different G-CSF regimens on neutropenia's incidence for patients treated by eribulin, to propose an optimal G-CSF dosing schedule. A population PK/PD model was developed to describe absolute neutrophil counts' (ANC) time course in 87 cancer patients receiving eribulin. The structural model considered ANC dynamics, neutropenic effect of eribulin and stimulating effect of G-CSF. Final model estimates were used to calculate neutropenia's incidence following different G-CSF dosing schedules for 1000 virtual subjects. The final model successfully described most of the ANC time course for all patients. Simulations showed that a single G-CSF administration 48 h after each eribulin injection reduced the risk of severe neutropenia from 29.7 to 5.2%. Five days of G-CSF only after the second eribulin injection or no G-CSF administration induces similar incidence of neutropenia. Simulations showed a single G-CSF administration 48 h after the end of each eribulin injection seems to be the optimal schedule to reduce eribulin-induced neutropenia. However, the new administration scheme should be tested in real life to evaluate its pertinence. Eudract 2015-001753-32, 2015/01/26.
Sections du résumé
BACKGROUND
Granulocyte colony-stimulating factors (G-CSF) are commonly given to limit chemotherapy-induced neutropenia, but, in case of weekly chemotherapy such as eribulin, their administration schedules remain empirical.
OBJECTIVES
This pharmacokinetic/pharmacodynamic (PK/PD) study was conducted to establish the effect of different G-CSF regimens on neutropenia's incidence for patients treated by eribulin, to propose an optimal G-CSF dosing schedule.
METHODS
A population PK/PD model was developed to describe absolute neutrophil counts' (ANC) time course in 87 cancer patients receiving eribulin. The structural model considered ANC dynamics, neutropenic effect of eribulin and stimulating effect of G-CSF. Final model estimates were used to calculate neutropenia's incidence following different G-CSF dosing schedules for 1000 virtual subjects.
RESULTS
The final model successfully described most of the ANC time course for all patients. Simulations showed that a single G-CSF administration 48 h after each eribulin injection reduced the risk of severe neutropenia from 29.7 to 5.2%. Five days of G-CSF only after the second eribulin injection or no G-CSF administration induces similar incidence of neutropenia.
CONCLUSION
Simulations showed a single G-CSF administration 48 h after the end of each eribulin injection seems to be the optimal schedule to reduce eribulin-induced neutropenia. However, the new administration scheme should be tested in real life to evaluate its pertinence.
TRIAL REGISTRATION
Eudract 2015-001753-32, 2015/01/26.
Identifiants
pubmed: 34997290
doi: 10.1007/s00280-021-04395-y
pii: 10.1007/s00280-021-04395-y
doi:
Substances chimiques
Antineoplastic Agents
0
Furans
0
Ketones
0
Granulocyte Colony-Stimulating Factor
143011-72-7
eribulin
LR24G6354G
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
197-208Subventions
Organisme : Eisai
ID : IIT
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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