PURPOSE: 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. PATIENTS AND 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.
PURPOSE: 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. PATIENTS AND 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: J G Coen van Hasselt; Anubha Gupta; Ziad Hussein; Jos H Beijnen; Jan H M Schellens; Alwin D R Huitema Journal: Br J Clin Pharmacol Date: 2013-09 Impact factor: 4.335
Authors: E Anders Kolb; Richard Gorlick; C Patrick Reynolds; Min H Kang; Hernan Carol; Richard Lock; Stephen T Keir; John M Maris; Catherine A Billups; Christopher Desjardins; Raushan T Kurmasheva; Peter J Houghton; Malcolm A Smith Journal: Pediatr Blood Cancer Date: 2013-03-28 Impact factor: 3.167
Authors: Antoinette R Tan; John Sarantopoulos; Lucy Lee; Larisa Reyderman; Yi He; Martin Olivo; Sanjay Goel Journal: Cancer Chemother Pharmacol Date: 2015-10-03 Impact factor: 3.333