Abstract
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/m(2) (except cycle 1 day 1, 1.4 mg/m(2)); severe, 0.7 mg/m(2); normal, 1.4 mg/m(2). 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/m(2) in patients with moderate or severe renal impairment achieved the same exposure as 1.4 mg/m(2) 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/m(2) in patients with moderate or severe renal impairment. CLINICALTRIALS. GOV IDENTIFIER: NCT01418677.