Improving cancer therapy by doxorubicin and granulocyte colony-stimulating factor: Insights from a computerized model of human granulopoiesis

V. Vainstein, Y. Ginosar, M. Shoham, A. Ianovski, A. Rabinovich, Y. Kogan, V. Selitser, Z. Agur

Research output: Contribution to journalArticlepeer-review

Abstract

Neutropenia is a significant dose-limiting toxicity of cancer chemotherapy, especially in dose-intensified regimens. It is widely treated by injections of Granulocyte Colony-Stimulating Factor (G-CSF). However, optimal schedules of G-CSF administration are still not determined. In order to aid in identifying more efficacious and less neutropenic treatment protocols, we studied a detailed physiologically-based computer model of granulopoiesis, as affected by different treatment schedules of doxorubicin and/or Granulocyte Colony-Stimulating Factor (G-CSF). We validated the model as evident from accurate prediction of clinical data on human granulopoiesis in healthy individuals and in doxorubicin-treated cancer patients, with or without G-CSF support. Based on our model, we suggest new G-CSF administration regimens. These regimens include reduced G-CSF doses, optimally timed post-chemotherapy. Application of these regimens can lead to minimization of G-CSF side effects, as well as more cost-effective and less myelotoxic protocols. Currently clinical trials are being designed in order to test these new treatment regimens.

Original languageEnglish
Pages (from-to)70-80
Number of pages11
JournalMathematical Modelling of Natural Phenomena
Volume1
Issue number2
DOIs
StatePublished - Jan 2006
Externally publishedYes

Keywords

  • chemotherapy
  • granulopoiesis
  • mathematical modeling
  • treatment optimization

ASJC Scopus subject areas

  • Modeling and Simulation
  • Applied Mathematics

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