Pharmacokinetics of eribulin mesylate in cancer patients with normal and impaired renal function

Antoinette R. Tan, John Sarantopoulos, Lucy Lee, Larisa Reyderman, Yi He, Martin Olivo, Sanjay Goel

Research output: Contribution to journalArticle

13 Citations (Scopus)

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/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.

Original languageEnglish (US)
Pages (from-to)1051-1061
Number of pages11
JournalCancer Chemotherapy and Pharmacology
Volume76
Issue number5
DOIs
StatePublished - Nov 1 2015

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eribulin
Pharmacokinetics
Creatinine
Kidney
Neoplasms
Toxicity
Confidence Intervals
Tumors

Keywords

  • Cancer patients
  • Eribulin
  • Pharmacokinetics
  • Renal function
  • Renal impairment

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

Pharmacokinetics of eribulin mesylate in cancer patients with normal and impaired renal function. / Tan, Antoinette R.; Sarantopoulos, John; Lee, Lucy; Reyderman, Larisa; He, Yi; Olivo, Martin; Goel, Sanjay.

In: Cancer Chemotherapy and Pharmacology, Vol. 76, No. 5, 01.11.2015, p. 1051-1061.

Research output: Contribution to journalArticle

Tan, Antoinette R. ; Sarantopoulos, John ; Lee, Lucy ; Reyderman, Larisa ; He, Yi ; Olivo, Martin ; Goel, Sanjay. / Pharmacokinetics of eribulin mesylate in cancer patients with normal and impaired renal function. In: Cancer Chemotherapy and Pharmacology. 2015 ; Vol. 76, No. 5. pp. 1051-1061.
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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/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.",
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AU - Tan, Antoinette R.

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AU - He, Yi

AU - Olivo, Martin

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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.

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