Characterization of Endogenous G-CSF and the Inverse Correlation to Chemotherapy-Induced Neutropenia in Patients with Breast Cancer Using Population Modeling
2014 (English)In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 31, no 12, 3390-3403 p.Article in journal (Refereed) Published
Neutropenia is a severe adverse-event of chemotherapeutics. Neutrophils (ANC) are mainly regulated by granulocyte colony stimulating factor (G-CSF). The aim was to characterize the dynamics between endogenous G-CSF and ANC over time following chemotherapy. Endogenous G-CSF and ANC were monitored in forty-nine breast cancer patients treated with sequential adjuvant 5-fluorouracil-epirubicin-cyclophosphamide and docetaxel. During treatment courses ANC was transiently decreased and was reflected in an endogenous G-CSF increase, which was well described by a semi-mechanistic model including control mechanisms; when G-CSF concentrations increased the proliferation rate increased and the bone maturation time reduced for ANC. Subsequently, ANC in the circulation increased leading to increased elimination of G-CSF. Additionally, a non-specific elimination for G-CSF was quantified. The ANC-dependent elimination contributed to 97% at baseline and 49% at an ANC of 0.1 center dot 10(9)/L to the total G-CSF elimination. The integrated G-CSF-myelosuppression model captured the initial rise in endogenous G-CSF following chemotherapy-induced neutropenia and the return to baseline of G-CSF and ANC. The model supported the self-regulatory properties of the system and may be a useful tool for further characterization of the biological system and in optimization of chemotherapy treatment.
Place, publisher, year, edition, pages
2014. Vol. 31, no 12, 3390-3403 p.
IdentifiersURN: urn:nbn:se:uu:diva-239349DOI: 10.1007/s11095-014-1429-9ISI: 000344790400014PubMedID: 24919931OAI: oai:DiVA.org:uu-239349DiVA: diva2:774831