PK/PD modeling of the effect of Escitalopram combined with Docetaxel in the treatment of breast cancer with depression in mice.

Depression is a common complication of breast cancer that negatively impacts prognosis. To explore the efficacy and dosage of antidepressant Escitalopram (ESC) alone or combined with chemotherapy drug Docetaxel (DOC) in breast cancer with comorbid depression, a depressed tumor-bearing mice model was established via chronic unpredictable mild stress (CUMS) and 4T1 cell inoculation. Depression-like behavior in mice intensified with increasing tumor volume, while depression facilitated the occurrence of breast cancer lung metastasis. ESC counteracted this effect and, when combined with DOC, further suppressed lung metastatic foci and reduced tumor volume. A disease progression model was developed to quantify the dynamics of depression status and tumor growth along with their mutually reinforcing effects, and a PK/PD model was further established to characterize the pharmacodynamic effects of ESC and DOC. The parameter ψ of the PK/PD model indicated that ESC and DOC cooperatively inhibit metastasis with a synergy index of 2.25, while simulation results suggested combination therapy with 2.5 mg/kg ESC (approximating the clinical dose) and DOC significantly outperformed DOC monotherapy in efficacy. This study provides a reference for the dosing regimen of ESC as an adjunctive therapy for breast cancer patients who suffer depression.