Tumor growth instability and its implications for chemotherapy

Cancer Res. 2009 Nov 1;69(21):8507-15. doi: 10.1158/0008-5472.CAN-09-0653. Epub 2009 Oct 27.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Antineoplastic Agents / therapeutic use*
  • Computer Simulation
  • Humans
  • Models, Biological*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology*
  • Treatment Outcome
  • Tumor Burden

Substances

  • Antineoplastic Agents