Kinetics of Minimal Residual Disease

Abstract

The development of a rational approach to adjuvant chemotherapy of cancer depends upon at least four factors:

• 1. Recognition that micrometastases are frequently disseminated and established prior to the time of surgery for a primary cancer;

• 2. Measurement (e.g., with biomarkers) or reliable estimates of the number of residual (and occult) clonogenic tumor cells remaining after surgery;

• 3. Knowledge of the kinetics behavior and drug sensitivity of small numbers of clonogenic cells;

• 4. Availability of effective anticancer drugs, particularly those that have a cell-cycle, nonspecific mode of action that will be lethal to quiescent cells as well as those undergoing proliferation.

In this analysis I will rely heavily on quantitative extrapolations relating to tumor kinetics and drug effects and select kinetic parameters characteristic of tumors that might be difficult to eradicate. This approach permits prediction of drug schedules and intensity of treatment that are likely necessary to eradicate the residual clonogenic tumor cell population. The Arizona Breast Cancer Adjuvant Program (results discussed elsewhere in this text) will be used to exemplify application of some of these principles.