USING COMPUTER SIMULATIONS FOR EVALUATING THE EFFICACY OF BREAST CANCER CHEMOTHERAPY PROTOCOLS

Abstract

The fundamental strategy of chemotherapy is to maximize tumor eradication within the limits of tolerable toxicity to the organism. To demonstrate the use of mathematical models in designing treatment protocols, we modeled the effect of chemotherapy on tumor mass and simulated the outcome of several neoadjuvant protocols for breast cancer disease. The model assumes unperturbed tumor growth, superimposed by periods of tumor regression during treatment applications. It takes into account both cell cycle specific (CCS) and cell-cycle non specific drugs (CCNS). Three possible modes of growth (exponential, Gompertz and power laws) were simulated in the study. The model parameters (such as cytotoxic activity of a given protocol) were estimated by best fit procedure from the clinical data of tumor regression following neoadjuvant treatments. The estimated parameters were then used to simulate various regimens that are employed today in the treatment of adjuvant and metastatic breast cancer. Our results suggest that although high dose chemotherapy (HDT) cannot eradicate overt metastatic disease, it may lead to cure if applied early in the natural history of breast cancer. Moreover, the simulations predict a better response for a rather toxic dose dense regimen, as compared to a more conventional protocol. However, our simulations suggest that a well tolerable continuous protocol is no less efficient. The results of the study provide insights into the effectivity of chemotherapy and may assist in designing better protocols.