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Updated: Jul 19, 2026
Isolation and Characterization of Neutrophils with Anti-Tumor Properties
Published on: June 19, 2015
Relationship between cytochrome 3A activity, inflammatory status and the risk of docetaxel-induced febrile
J Alexandre1, E Rey2, V Girre3
1Department of Medical Oncology, Groupe Hospitalier Cochin St Vincent de Paul, Université Paris 5, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Molecular Pathology, University of Texas, MD Anderson Cancer Center, Houston, USA.
Background:
We hypothesized that cancer-related inflammation might increase the risk of febrile neutropenia (FN) induced by docetaxel (DCX, Taxotere), by both affecting the exposure to DCX and the tissue sensitivity.
Patients And Methods:
Advanced cancer patients with normal liver function, performance status (PS)<3, were included. Cytochrome P450 3A (CYP 3A) activity was estimated before the first cycle of DCX by a single determination of midazolam plasma concentration, 4 hours after 0.015 mg/kg i.v. bolus. Following the first cycle of 75-100 mg/m2 DCX, clearance and area under the concentration versus time curve (AUC) were estimated using a limited sampling strategy.
Results:
Among 56 assessable patients, 7 FNs occurred after first cycle (13%). In univariate analysis, high midazolam concentration and free DCX AUC were associated with severe neutropenia and FN. In addition to DCX exposure-related parameters, the risk of FN was also correlated with poor PS, baseline lymphopenia and lung cancer, while high ferritin level, indicator of an inflammatory state, reached borderline significance (P=0.07). By multivariate analysis, total DCX AUC and baseline lymphopenia were associated with FN. High midazolam concentration was correlated with elevated ferritin level (r=0.32; P=0.02).
Conclusion:
Inflammatory status and lymphocyte count should be included in the evaluation of the benefice/risk ratio before the initiation of DCX.
