Systems Biology Mathematical Oncology Tumor Growth Instability and Its Implications for Chemotherapy

Optimal delivery of chemotherapy intensity is dependent on hostand tumor-specific characteristics. In this article, the chemotherapy late intensity schedule is revised to account for tumor growth instability, where a small tumor cell fraction emerges that exhibits a higher proliferation rate than the parent strain. Modeling this instability as simplified twopopulation dynamics, we find that: (a) if this instability precedes the onset of treatment, the slope of the linear increase of the drug concentration for the standard “NortonSimon late intensity schedule” changes and the initial value of the dose strongly depends on the ratio of the two tumor cell populations and on their distinct growth rates; and (b) if the instability trails the initial treatment, the effective chemotherapeutic drug concentration changes as well. Both cases point toward testable potential refinements of the Norton-Simon late intensity schedule. [Cancer Res 2009;69(21):8507–15]