Tumor‐in‐host DEB‐TGI model for EGFR‐TKI (gefitinib single‐agent treated group)

EGFR‐TKIs, such as gefitinib, target processes that are involved in tumor growth and progression, including proliferation, apoptosis, and angiogenesis. 39 , 40 Based on this information, the gefitinib single‐agent model hypothesis is a double anticancer drug effect. First, a direct killing effect on tumor cells (cytotoxic effect) is implemented as a reduction of tumor growth function proportional to drug concentration, Cgeft, and to proliferating tumor cell mass, Vut:

where the parameter k2,gef represents the gefitinib cytotoxic potency.

Second, a cytostatic effect, accounting for gefitinib ability in reducing tumor survival and proliferation, is modeled through an inhibitory maximum unbound systemic concentration ( Imax) function on tumor aggressiveness, μu, governing kut:

where μu,b is the tumor gluttony in absence of treatment and IC50,gef the gefitinib concentration exerting the 50% of the maximal inhibitory effect, Imax. From Equation 2e and Equation 4, this cytostatic effect results in a reduction of tumor energy flow that leads to a tumor growth modulation.

In accordance with experimental mice body weight data, no direct pharmacological effect on host organism is modeled.