title: Pharmacokinetics of eribulin mesylate in patients with solid tumors and hepatic impairment.
abstract: OBJECTIVE
  The aim of this study was to determine the plasma pharmacokinetics of eribulin mesylate in patients with solid tumors with mild and moderate hepatic impairment.
  
  
  METHODS
  A phase I, pharmacokinetic study was performed in patients with advanced solid tumors and normal hepatic function or Child-Pugh A (mild) or Child-Pugh B (moderate) hepatic impairment. Treatments were given on day 1 and 8 of a 21-day cycle and consisted of 1.4, 1.1 and 0.7 mg/m(2) eribulin mesylate, for normal hepatic function, Child-Pugh A and B hepatic impairment, respectively. Also safety and anti-tumor activity were determined.
  
  
  RESULTS
  Hepatic impairment increased exposure to eribulin. In patients with Child-Pugh A (N = 7) and Child-Pugh B (N = 5), mean dose-normalized AUC(0-∞) was 1.75-fold (90 % confidence intervals (CI): 1.16-2.65) and 2.48-fold (90 % CI: 1.57-3.92) increased, respectively, compared with patients who have normal function (N = 6). The most frequently reported treatment-related events were alopecia (12/18) and fatigue (7/18) and these were observed across all groups. Nine patients (50 %) had stable disease as best response.
  
  
  CONCLUSIONS
  A reduced dose of 1.1 and 0.7 mg/m(2) of eribulin mesylate is recommended for patients with Child-Pugh A or B hepatic impairment, respectively.
authors.affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: L A
authors.initials: LA
authors.lastname: Devriese
authors.forename: P O
authors.initials: PO
authors.lastname: Witteveen
authors.forename: S
authors.initials: S
authors.lastname: Marchetti
authors.forename: M
authors.initials: M
authors.lastname: Mergui-Roelvink
authors.forename: L
authors.initials: L
authors.lastname: Reyderman
authors.forename: J
authors.initials: J
authors.lastname: Wanders
authors.forename: A
authors.initials: A
authors.lastname: Jenner
authors.forename: G
authors.initials: G
authors.lastname: Edwards
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: E E
authors.initials: EE
authors.lastname: Voest
authors.forename: J H M
authors.initials: JH
authors.lastname: Schellens
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004334:Drug Administration Schedule; D005260:Female; D005663:Furans / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D048550:Hepatic Insufficiency / Q000150:complications / Q000378:metabolism*; D006801:Humans; D007659:Ketones / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D009426:Netherlands; D016896:Treatment Outcome; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D007659:Ketones; C490954:eribulin; D000095662:Polyether Polyketides