RESUMEN
A mathematical model is presented to investigate the relationship between drug order and treatment response in gastric cancer chemotherapy involving a taxane (either paclitaxel or docetaxel) coupled with flavopiridol. To model treatment effects, we simulate treatment by bolus injection and employ a pulsing condition to indicate cell kill as well as instantaneous changes to the cell's transition rates. Cell population growth is described using an ordinary differential equation model whereby we examine the treatment effects upon cells in various stages of the cell cycle. Ultimately, the results generated support prior clinical investigations which indicate that for an enhanced synergistic effect, flavopiridol must be administered following taxane therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Hidrocarburos Aromáticos con Puentes/farmacología , Ciclo Celular/efectos de los fármacos , Flavonoides/farmacología , Modelos Biológicos , Piperidinas/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Taxoides/farmacología , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacología , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Simulación por Computador , Flavonoides/administración & dosificación , Humanos , Piperidinas/administración & dosificación , Taxoides/administración & dosificaciónRESUMEN
A mathematical model is presented to investigate the ordering phenomenon observed in the comparison of alternating to sequential regimens of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) and doxorubicin used in breast cancer chemo-therapy. The ordinary differential equation model incorporates cell cycle specificity and resistance to study why doses of the same drugs given in different orders result in different clinical outcomes. The model employs a pulsing condition to simulate treatment and induced resistance, and we investigate treatment outcome by simulating a patient population by varying parameters using uniform distributions. The results of these simulations correspond to those observed in prior clinical studies and suggest that drug resistance might be a key mechanism in the sequential regimen's superiority.