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 - 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 -