Epirubicin in patients with liver dysfunction: development and evaluation of a novel dose modification scheme

• Published in: European journal of cancer (1990) 2003-03, Vol.39 (5), p.580-586
• Main Authors: Dobbs, N.A, Twelves, C.J, Gregory, W, Cruickshanka, C, Richards, M.A, Rubens, R.D
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacokinetics; Area Under Curve; Aspartate Aminotransferases - blood; Breast Cancer; Breast Neoplasms - drug therapy; Chemotherapy; Drug Administration Schedule; Epirubicin; Epirubicin - administration & dosage; Epirubicin - pharmacokinetics; Female; Humans; Liver Diseases - complications; Liver Diseases - enzymology; Liver Diseases - metabolism; Liver dysfunction; Middle Aged; Pharmacokinetics; Treatment Outcome
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(02)00669-X

This study aimed to develop an epirubicin dose modification scheme in women with breast cancer and liver dysfunction. We first identified target areas under the concentration-time curve (AUCs) of 2400 and 1600 ng/ml.h from pharmacokinetic studies in 15 women with normal liver tests. In a second group of 16 women with abnormal liver biochemistry, the relationship between raised asparate aminotransferase (AST) and epirubicin clearance was: dose=AUC (97.5−34.2×log AST). Adaptive dosing was evaluated prospectively in a third group of 41 women with serum AST ⩾2×normal±raised bilirubin. The median AUCs were 2444 and 1608 ng/ml.h, close to the high and low target AUCs, respectively. Variability in AUC was lower with adaptive dosing than in a fourth group given an unadjusted dose of epirubicin (coefficient of variation=25.8, 30.0 and 46.5%, respectively; P=0.06). Epirubicin dosing based on AST is safe and may reduce pharmacokinetic variability.