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.