Neutrophil dynamics during concurrent chemotherapy and @entity1261 administration: Mathematical modelling guides dose optimisation to minimise XXXX .

@entity1 @entity1398 @entity137 @entity1261
UNASSIGNED: The choice of chemotherapy regimens is often constrained by the @entity1 's tolerance to the side effects of chemotherapeutic agents. This dose-limiting issue is a major concern in dose regimen design, which is typically focused on maximising drug benefits. Chemotherapy-induced @entity1398 is one of the most prevalent @entity137 effects @entity1 experience and frequently threatens the efficient use of chemotherapy. In response, @entity1261 ( @entity1261 ) is co-administered during chemotherapy to stimulate neutrophil production, increase neutrophil counts, and hopefully avoid @entity1398 . Its clinical use is, however, largely dictated by trial and error processes. Based on up-to-date knowledge and rational considerations, we develop a physiologically realistic model to mathematically characterise the neutrophil production in the bone marrow which we then integrate with pharmacokinetic and pharmacodynamic (PKPD) models of a chemotherapeutic agent and an exogenous form of @entity1261 (recombinant @entity1 @entity1261 , or rhG-CSF). In this work, model parameters represent the average values for a general @entity1 and are extracted from the literature or estimated from available data. The dose effect predicted by the model is confirmed through previously published data. Using our model, we were able to determine clinically relevant dosing regimens that advantageously reduce the number of rhG-CSF administrations compared to original studies while significantly improving the @entity1398 status. More particularly, we determine that it could be beneficial to delay the first administration of rhG-CSF to day seven post-chemotherapy and reduce the number of administrations from ten to three or four for a @entity1 undergoing 14-day periodic chemotherapy.
