Annals of Oncology Advance Access published online on October 23, 2006
Annals of Oncology, doi:10.1093/annonc/mdl321
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1 Department 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
* To whom correspondence should be addressed. 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.
Received June 13, 2006
Revised July 28, 2006
Accepted August 2, 2006
original article
Relationship between cytochrome 3A activity, inflammatory status and the risk of docetaxel-induced febrile neutropenia: a prospective study
J. Alexandre 1 *, E. Rey 2, V. Girre 3, S. Grabar 4, A. Tran 2, V. Montheil 5, F. Rabillon 5, V. Dieras 3, V. Jullien 2, P. Hérait 5, G. Pons 2, J.-M. Treluyer 2, and F. Goldwasser 5
2 Department of Clinical Pharmacology, Groupe Hospitalier Cochin St Vincent de Paul, Université Paris 5, Assistance Publique--Hôpitaux de Paris, Paris, France
3 Department of Medical Oncology, Institut Curie, Paris, France
4 Department of Biostatistics, Groupe Hospitalier Cochin St Vincent de Paul, Université Paris 5, Assistance Publique--Hôpitaux de Paris, Paris, France
5 Department of Medical Oncology, Groupe Hospitalier Cochin St Vincent de Paul, Université Paris 5, Assistance Publique--Hôpitaux de Paris, Paris, France
J. Alexandre, E-mail: jalexand{at}mdanderson.org
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