A randomized study of epirubicin at four different dose levels in advanced breast cancer. Feasibility of myelotoxicity prediction through single blood-sample measurement.
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 less than 0.001) or epirubicin and epirubicinol together (r = -0.63, P less than 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 x c6 (ng/ml)-0.14.
Institute of Pharmacology, University of Aarhus, Denmark.
P
P
Jakobsen
L
L
Bastholt
M
M
Dalmark
P
P
Pfeiffer
D
D
Petersen
S B
SB
Gjedde
E
E
Sandberg
C
C
Rose
O S
OS
Nielsen
H T
HT
Mouridsen
D001853:Bone Marrow / Q000187:drug effects*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000097:blood; D015251:Epirubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D011379:Prognosis; D012044:Regression Analysis; D013997:Time Factors
D015251:Epirubicin; D004317:Doxorubicin; C046579:4'-deoxydoxorubicinol