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Improving CancerTherapy by Doxorubicin and Granulocyte Colony-Stimulating Factor: Insights from a Computerized Model of Human Granulopoiesis

Published online by Cambridge University Press:  15 May 2008

V. Vainstein*
Affiliation:
Institute for Medical Biomathematics (IMBM), POB 282 Hate'ena 10, Bene Ataroth, 60991 Israel
Y. Ginosar
Affiliation:
Institute for Medical Biomathematics (IMBM), POB 282 Hate'ena 10, Bene Ataroth, 60991 Israel
M. Shoham
Affiliation:
Optimata Ltd, 7 Abba Hillel Silver St., Ramat-Gan, 52522 Israel
A. Ianovski
Affiliation:
Optimata Ltd, 7 Abba Hillel Silver St., Ramat-Gan, 52522 Israel
A. Rabinovich
Affiliation:
Optimata Ltd, 7 Abba Hillel Silver St., Ramat-Gan, 52522 Israel
Y. Kogan
Affiliation:
Institute for Medical Biomathematics (IMBM), POB 282 Hate'ena 10, Bene Ataroth, 60991 Israel
V. Selitser
Affiliation:
Institute for Medical Biomathematics (IMBM), POB 282 Hate'ena 10, Bene Ataroth, 60991 Israel
Z. Agur
Affiliation:
Institute for Medical Biomathematics (IMBM), POB 282 Hate'ena 10, Bene Ataroth, 60991 Israel Optimata Ltd, 7 Abba Hillel Silver St., Ramat-Gan, 52522 Israel
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Abstract

Neutropenia is a significant dose-limiting toxicity of cancerchemotherapy, especially in dose-intensified regimens. It iswidely treated by injections of Granulocyte Colony-StimulatingFactor (G-CSF). However, optimal schedules of G-CSF administrationare still not determined. In order to aid in identifying moreefficacious and less neutropenic treatment protocols, we studied adetailed physiologically-based computer model of granulopoiesis,as affected by different treatment schedules of doxorubicin and/orGranulocyte Colony-Stimulating Factor (G-CSF). We validated themodel as evident from accurate prediction of clinical data onhuman granulopoiesis in healthy individuals and indoxorubicin-treated cancer patients, with or without G-CSFsupport. Based on our model, we suggest new G-CSF administrationregimens. These regimens include reduced G-CSF doses, optimallytimed post-chemotherapy. Application of these regimens can lead tominimization of G-CSF side effects, as well as more cost-effectiveand less myelotoxic protocols. Currently clinical trials are beingdesigned in order to test these new treatment regimens.

Type
Research Article
Copyright
© EDP Sciences, 2006

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