A RANDOMIZED STUDY OF EPIRUBICIN AT 4 DIFFERENT DOSE LEVELS IN ADVANCED BREAST-CANCER - FEASIBILITY OF MYELOTOXICITY PREDICTION THROUGH SINGLE BLOOD-SAMPLE MEASUREMENT

被引:55
作者
JAKOBSEN, P
BASTHOLT, L
DALMARK, M
PFEIFFER, P
PETERSEN, D
GJEDDE, SB
SANDBERG, E
ROSE, C
NIELSEN, OS
MOURIDSEN, HT
机构
[1] DANISH CANC SOC,CLIN RES SECT,AARHUS,DENMARK
[2] ESBJERG CENT HOSP,DEPT ONCOL,ESBJERG,DENMARK
[3] AARHUS UNIV HOSP,DEPT ONCOL,DK-8000 AARHUS,DENMARK
[4] RIGSHOSP,DEPT ONCOL,DK-2100 COPENHAGEN,DENMARK
[5] ODENSE UNIV HOSP,DEPT ONCOL,DK-5000 ODENSE,DENMARK
关键词
EPIRUBICIN; MYELOTOXICITY; PHARMACOKINETICS; PHARMACODYNAMICS;
D O I
10.1007/BF00685824
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 < 0.00 1). 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 WBC(nadir) = log WBC(initial) - 0.0073 X c6 (ng/ml) -0.14.
引用
收藏
页码:465 / 469
页数:5
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