TY - JOUR
T1 - Pharmacokinetics of eribulin mesylate in cancer patients with normal and impaired renal function
AU - Tan, Antoinette R.
AU - Sarantopoulos, John
AU - Lee, Lucy
AU - Reyderman, Larisa
AU - He, Yi
AU - Olivo, Martin
AU - Goel, Sanjay
N1 - Funding Information:
We thank the study site investigators Dr. A. Wang-Gillam (Siteman Cancer Center, Washington University, St Louis, MO, USA), Dr. V. Chung (City of Hope National Medical Centre, Duarte, CA, USA), and Dr. R.D. Harvey (Winship Cancer Institute, Emory University, Atlanta, GA, USA) for their contribution. The authors from the University of Texas Health Science Center San Antonio would also like to acknowledge a Cancer Center support grant from the Institute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio, San Antonio, TX (Grant: P30CA054174).
Funding Information:
A.R.T. and S.G. have received research funding from Eisai Inc.; L.R. and M.O. are employees of Eisai Inc.; L.L. and Y.H. were employees of Eisai Inc. at the time of manuscript preparation. J.S. declares no conflict of interest in relation to this manuscript. J.S. has received funding at the Institute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio, San Antonio, TX, USA, from Cancer Center Support Grant P30CA054174.
Publisher Copyright:
© 2015 The Author(s).
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Purpose: To evaluate the effect of renal impairment on eribulin mesylate pharmacokinetics following a single dose in adults with advanced solid tumors. Methods: Patients were grouped by renal function: moderate impairment (creatinine clearance [CrCl] 30-50 mL/min), severe impairment (CrCl 15-29 mL/min), or normal (CrCl ≥80 mL/min). During each 21-day cycle, eribulin mesylate doses (days 1 and 8) were administered intravenously: moderate, 1.1 mg/m2 (except cycle 1 day 1, 1.4 mg/m2); severe, 0.7 mg/m2; normal, 1.4 mg/m2. Results: Nineteen patients were enrolled (normal, n = 6; moderate, n = 7; severe, n = 6). Renal impairment was associated with an increased mean dose-normalized area under the concentration-time curve (ratios for moderate/normal and severe/normal: 1.49; 90 % confidence interval [CI] 0.9, 2.45). CrCl and renal function correlated positively, with a numerically small slope (0.0184; 90 % CI -0.00254, 0.0394). A simulated dose reduction to eribulin 1.1 mg/m2 in patients with moderate or severe renal impairment achieved the same exposure as 1.4 mg/m2 in those with normal renal function. All groups had similar toxicity profiles, with no unexpected adverse events. Conclusions: Renal impairment decreased eribulin clearance and increased exposure. Pharmacokinetic evaluation supports an eribulin dose reduction to 1.1 mg/m2 in patients with moderate or severe renal impairment. ClinicalTrials.gov Identifier: NCT01418677.
AB - Purpose: To evaluate the effect of renal impairment on eribulin mesylate pharmacokinetics following a single dose in adults with advanced solid tumors. Methods: Patients were grouped by renal function: moderate impairment (creatinine clearance [CrCl] 30-50 mL/min), severe impairment (CrCl 15-29 mL/min), or normal (CrCl ≥80 mL/min). During each 21-day cycle, eribulin mesylate doses (days 1 and 8) were administered intravenously: moderate, 1.1 mg/m2 (except cycle 1 day 1, 1.4 mg/m2); severe, 0.7 mg/m2; normal, 1.4 mg/m2. Results: Nineteen patients were enrolled (normal, n = 6; moderate, n = 7; severe, n = 6). Renal impairment was associated with an increased mean dose-normalized area under the concentration-time curve (ratios for moderate/normal and severe/normal: 1.49; 90 % confidence interval [CI] 0.9, 2.45). CrCl and renal function correlated positively, with a numerically small slope (0.0184; 90 % CI -0.00254, 0.0394). A simulated dose reduction to eribulin 1.1 mg/m2 in patients with moderate or severe renal impairment achieved the same exposure as 1.4 mg/m2 in those with normal renal function. All groups had similar toxicity profiles, with no unexpected adverse events. Conclusions: Renal impairment decreased eribulin clearance and increased exposure. Pharmacokinetic evaluation supports an eribulin dose reduction to 1.1 mg/m2 in patients with moderate or severe renal impairment. ClinicalTrials.gov Identifier: NCT01418677.
KW - Cancer patients
KW - Eribulin
KW - Pharmacokinetics
KW - Renal function
KW - Renal impairment
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U2 - 10.1007/s00280-015-2878-5
DO - 10.1007/s00280-015-2878-5
M3 - Article
C2 - 26433580
AN - SCOPUS:84944729266
SN - 0344-5704
VL - 76
SP - 1051
EP - 1061
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 5
ER -
