Mathematical Modelling of Natural Phenomena
- Mathematical Modelling of Natural Phenomena 2006 1 (02) : pp 70-80
- © EDP Sciences, 2006
- DOI: 10.1051/mmnp:2008003 (About DOI)
- Published online by Cambridge University Press: 01 February 2011
Research Article
Improving Cancer Therapy by Doxorubicin and Granulocyte Colony-Stimulating Factor: Insights from a Computerized Model of Human Granulopoiesis
V. Vainsteina1, Y. Ginosara1, M. Shohama2, A. Ianovskia2, A. Rabinovicha2, Y. Kogana1, V. Selitsera1 and Z. Agura1a2
a1 Institute for Medical Biomathematics (IMBM), POB 282 Hate'ena 10, Bene Ataroth, 60991 Israel
a2 Optimata Ltd, 7 Abba Hillel Silver St., Ramat-Gan, 52522 Israel
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.
(Online publication May 15 2008)
Key Words:
- mathematical modeling;
- granulopoiesis;
- chemotherapy;
- treatment optimization
Mathematics Subject Classification:
- 92C50;
- 92C45;
- 35Q80
Correspondence:
