A randomized study of epirubicin at four different dose levels in advanced breast cancer. Feasibility of myelotoxicity prediction through single blood-sample measurement |
| |
Authors: | Preben Jakobsen Lars Bastholt Mads Dalmark Per Pfeiffer Dorthe Petersen Susanne B Gjedde Erik Sandberg Carsten Rose Ole S Nielsen Henning T Mouridsen |
| |
Institution: | (1) Department of Oncology, Odense University Hospital, Odense, Denmark;(2) Department of Oncology, Rigshospitalet, Copenhagen, Denmark;(3) Department of Oncology, Aarhus University Hospital and Danish Cancer Society, Section of Clinical Research, Aarhus, Denmark;(4) Department of Oncology, Esbjerg Hospital, Esbjerg, Denmark;(5) Institute of Pharmacology, University of Aarhus, The Bartholin Building, DK-8000 Aarhus C, Denmark |
| |
Abstract: | Summary Detailed pharmacokinetic analysis and subsequent evaluation of myelotoxicity were performed in 55 patients who had been randomized to 4 different doses of epirubicin (40, 60, 90 or 135 mg/m2 given i.v. every 3 weeks). A significantly positive correlation was demonstrated between the AUC and the myelotoxicity of epirubicin. A similar correlation was observed when the metabolite epirubicinol was also considered. The decrease in leucocyte count as expressed by the logarithmic ratio between nadir WBC and initial WBC was linearly correlated with the AUC of either epirubicin alone (r=–0.55,P<0.001) or epirubicin and epirubicinol together (r=–0.63,P<0.001). As a relationship between the concentration of epirubicin in a single plasma sample taken at 6 h following i.v. administration and the AUC of the drug has been established, a log-linear relationship between the expected decrease in leucocytes and the concentration at 6 h after administration could be calculated. The proposed model is expressed as the equation: log WBCnadir=log WBCinitial–0.0073×c
6 (ng/ml) –0.14.This work was supported by the Lundbeck Foundation, the Michaelsen Foundation and Farmitalia Carlo Erba Ltd. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|