Math. Model. Nat. Phenom.
Volume 1, Number 2, 2006Hematopoiesis and blood diseases
|Page(s)||70 - 80|
|Published online||15 May 2008|
Improving Cancer Therapy by Doxorubicin and Granulocyte Colony-Stimulating Factor: Insights from a Computerized Model of Human Granulopoiesis
Institute for Medical Biomathematics (IMBM), POB
282 Hate'ena 10,
Bene Ataroth, 60991 Israel
2 Optimata Ltd, 7 Abba Hillel Silver St., Ramat-Gan, 52522 Israel
Corresponding author: firstname.lastname@example.org
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.
Mathematics Subject Classification: 92C50 / 92C45 / 35Q80
Key words: mathematical modeling / granulopoiesis / chemotherapy / treatment optimization
© EDP Sciences, 2006
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