Tumor growth instability and its implications for chemotherapy.
Optimal delivery of chemotherapy intensity is dependent on host- and 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 two-population 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 "Norton-Simon 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.
Castorina
Paolo
P
Dipartimento di Fisica, Università di Catania, Istituto Nazionale Fisica Nucleare-Catania, and Centro Siciliano Fisica Nucleare e Struttura della Materia, Catania, Italy. paolo.castorina@ct.infn.it
Carcò
Daniela
D
Guiot
Caterina
C
Deisboeck
Thomas S
TS
D000465:Algorithms; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome; D047368:Tumor Burden
D000970:Antineoplastic Agents