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Characterization of...
Characterization of Endogenous G-CSF and the Inverse Correlation to Chemotherapy-Induced Neutropenia in Patients with Breast Cancer Using Population Modeling
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- Quartino, Angelica L. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Karlsson, Mats O. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Lindman, Henrik (författare)
- Uppsala universitet,Enheten för onkologi
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- Friberg, Lena E. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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(creator_code:org_t)
- 2014-06-12
- 2014
- Engelska.
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 31:12, s. 3390-3403
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
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