Abstract 1707P
Background
Granulocyte colony-stimulating factors (G-CSF) are commonly given to limit chemotherapy-induced neutropenia. However, for weekly chemotherapy such as eribulin, their administration schedules remain empirical. A 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. Additionally, in a real-life setting, the best G-CSF dosing schedule was compared, in a small subset of patients, to the most frequently used.
Methods
A semi-physiological population PK/PD neutropoiesis model was developed from absolute neutrophil counts (ANC) obtained in 87 cancer patients receiving eribulin for two cycles. The structural model considered ANC dynamics, neutropenic effect of eribulin and the stimulating effect of G-CSF on neutrophils. Final model parameters were used to calculate the incidence of neutropenia following different G-CSF dosing schedules for 1’000 virtual subjects. Then, all consecutive patients of our institution were followed-up for the first cycle to evaluate the risk of neutropenia.
Results
The final model successfully described the ANC time-course for all patients. Simulations showed that a single G-CSF administration 48h after each eribulin injection reduced the risk of severe neutropenia from 29.7% to 5.2%. This G-CSF dosing schedule was compared to other schedules in 27 consecutive patients treated with eribulin. Out of these patients, 10 received a single G-CSF injection 48h after each eribulin injection, whereas 16 received longer duration of treatment and 1 patient did not receive G-CSF. Only 1 out of 10 patients with the new G-CSF dosing schedule experienced a grade II neutropenia, while 2 out of 16 of the other patients experienced a neutropenia (grade I and II). The patient without G-CSF experienced a grade II neutropenia.
Conclusions
The PK/PD model well described our population's ANC data. Simulations showed a single G-CSF administration 48 hours after the end of each chemotherapy seems to be the optimal schedule to reduce neutropenia. In a real-life setting, we have shown, in a small subset of patients, that decreasing the number of G-CSF injections was not deleterious.
Clinical trial identification
EudraCT 2015-001753-32.
Editorial acknowledgement
Legal entity responsible for the study
Centre Georges-François Leclerc.
Funding
Centre Georges-François Leclerc, Eisai.
Disclosure
G. Freyer: Financial Interests, Institutional, Invited Speaker: Eisai. All other authors have declared no conflicts of interest.