title: Epirubicin in patients with liver dysfunction: development and evaluation of a novel dose modification scheme.
abstract: 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 (97.5-34.2xlog AST). Adaptive dosing was evaluated prospectively in a third group of 41 women with serum AST > or =2xnormal+/-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.
authors.affiliation: Breast Oncology Unit, GKT School of Medicine, Guy's Hospital, London, UK.
authors.forename: N A
authors.initials: NA
authors.lastname: Dobbs
authors.forename: C J
authors.initials: CJ
authors.lastname: Twelves
authors.forename: W
authors.initials: W
authors.lastname: Gregory
authors.forename: C
authors.initials: C
authors.lastname: Cruickshanka
authors.forename: M A
authors.initials: MA
authors.lastname: Richards
authors.forename: R D
authors.initials: RD
authors.lastname: Rubens
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000150:complications / Q000201:enzymology / Q000378:metabolism*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D001219:Aspartate Aminotransferases