FRIDAY, October 20, 2006
Time: 2:00 PM
Constant Hall 1043

Title: A Microenvironment Based Model of Antimitotic Therapy of a Gompertz Growth Tumor

Frank P. Kosusko
Hampton University

A model of tumor growth, based on two-compartment cancer population dynamics, and an overall Gompertzian growth has been previously developed. The main feature of the model is an inter-compartmental transfer function that describes the net exchange between proliferating (P) and quiescent (Q) cells and yields Gompertzian growth for tumor cell population N = P + Q. Model parameters provide for cell reproduction and cell death. This model is further developed here and modified to simulate antimitotic therapy. The therapy decreases the reproduction rate constant and increases the death rate constant of proliferating cells with no direct effect on quiescent cells. The model results in a system of two ODE equations (in N and P/N) which has an analytical solution.

Net tumor growth depends on support from the microenvironment. Indirectly, this is manifested in the transfer function which depends on the proliferation ratio, P/N. Antimitotic therapy will change P/N, and the microenvironment responds by slowing the transfer rate from P to Q. While the cellular effects of therapy are modeled as dependent only on antimitotic activity of the drug, the tumor response also depends on the tumor age and any previous therapies - after the first therapy, it is not the same tumor.

The strength of therapy is simulated by parameter, the ratio of therapy induced net proliferation rate constant versus the original. A pharmacokinetic factor inversely proportional to tumor size is implemented. Various chemotherapy regimens are simulated and the outcomes of therapy administered at different time points in the life history of the tumor are explored. Our analysis shows: 1) for a constant total dose administered, a decreasing dose schedule is marginally superior to an increasing or constant scheme, with more pronounced benefit for faster growing tumors, 2) younger tumors require a higher dose to stop the growth - the minimum dose to stop tumor growth is age dependent, and 3) a dose dense schedule is favored. Faster growing tumors respond better to dose density.