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A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function
PURPOSE: Limited data are available on cabazitaxel pharmacokinetics in patients with renal impairment. This open-label, multicenter study assessed cabazitaxel in patients with advanced solid tumors and normal or impaired renal function. METHODS: Cohorts A (normal renal function: creatinine clearance...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114328/ https://www.ncbi.nlm.nih.gov/pubmed/27796539 http://dx.doi.org/10.1007/s00280-016-3175-7 |
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author | Azaro, Analía Rodón, Jordi Machiels, Jean-Pascal Rottey, Sylvie Damian, Silvia Baird, Richard Garcia-Corbacho, Javier Mathijssen, Ron H. J. Clot, Pierre-François Wack, Claudine Shen, Liji de Jonge, Maja J. A. |
author_facet | Azaro, Analía Rodón, Jordi Machiels, Jean-Pascal Rottey, Sylvie Damian, Silvia Baird, Richard Garcia-Corbacho, Javier Mathijssen, Ron H. J. Clot, Pierre-François Wack, Claudine Shen, Liji de Jonge, Maja J. A. |
author_sort | Azaro, Analía |
collection | PubMed |
description | PURPOSE: Limited data are available on cabazitaxel pharmacokinetics in patients with renal impairment. This open-label, multicenter study assessed cabazitaxel in patients with advanced solid tumors and normal or impaired renal function. METHODS: Cohorts A (normal renal function: creatinine clearance [CrCL] >80 mL/min/1.73 m(2)), B (moderate renal impairment: CrCL 30 to <50 mL/min/1.73 m(2)) and C (severe impairment: CrCL <30 mL/min/1.73 m(2)) received cabazitaxel 25 mg/m(2) (A, B) or 20 mg/m(2) (C, could be escalated to 25 mg/m(2)), once every 3 weeks. Pharmacokinetic parameters and cabazitaxel unbound fraction (F (U)) were assessed using linear regression and mixed models. Geometric mean (GM) and GM ratios (GMRs) were determined using mean CrCL intervals (moderate and severe renal impairment: 40 and 15 mL/min/1.73 m(2)) versus a control (90 mL/min/1.73 m(2)). RESULTS: Overall, 25 patients received cabazitaxel (median cycles: 3 [range 1–20]; Cohort A: 5 [2–13]; Cohort B: 3 [1–15]; and Cohort C: 5 [1–20]), of which 24 were eligible for pharmacokinetic analysis (eight in each cohort). For moderate and severe renal impairment versus normal renal function, GMR estimates were: clearance normalized to body surface area (CL/BSA) 0.95 (90% CI 0.80–1.13) and 0.89 (0.61–1.32); area under the curve normalized to dose (AUC/dose) 1.06 (0.88–1.27) and 1.14 (0.76–1.71); and F (U) 0.99 (0.94–1.04) and 0.97 (0.87–1.09), respectively. Estimated slopes of linear regression of log parameters versus log CrCL (renal impairment) were: CL/BSA 0.06 (−0.15 to 0.28); AUC/dose −0.07 (−0.30 to 0.16); and F (U) 0.02 (−0.05 to 0.08). Cabazitaxel safety profile was consistent with previous reports. CONCLUSIONS: Renal impairment had no clinically meaningful effect on cabazitaxel pharmacokinetics. |
format | Online Article Text |
id | pubmed-5114328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-51143282016-12-02 A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function Azaro, Analía Rodón, Jordi Machiels, Jean-Pascal Rottey, Sylvie Damian, Silvia Baird, Richard Garcia-Corbacho, Javier Mathijssen, Ron H. J. Clot, Pierre-François Wack, Claudine Shen, Liji de Jonge, Maja J. A. Cancer Chemother Pharmacol Original Article PURPOSE: Limited data are available on cabazitaxel pharmacokinetics in patients with renal impairment. This open-label, multicenter study assessed cabazitaxel in patients with advanced solid tumors and normal or impaired renal function. METHODS: Cohorts A (normal renal function: creatinine clearance [CrCL] >80 mL/min/1.73 m(2)), B (moderate renal impairment: CrCL 30 to <50 mL/min/1.73 m(2)) and C (severe impairment: CrCL <30 mL/min/1.73 m(2)) received cabazitaxel 25 mg/m(2) (A, B) or 20 mg/m(2) (C, could be escalated to 25 mg/m(2)), once every 3 weeks. Pharmacokinetic parameters and cabazitaxel unbound fraction (F (U)) were assessed using linear regression and mixed models. Geometric mean (GM) and GM ratios (GMRs) were determined using mean CrCL intervals (moderate and severe renal impairment: 40 and 15 mL/min/1.73 m(2)) versus a control (90 mL/min/1.73 m(2)). RESULTS: Overall, 25 patients received cabazitaxel (median cycles: 3 [range 1–20]; Cohort A: 5 [2–13]; Cohort B: 3 [1–15]; and Cohort C: 5 [1–20]), of which 24 were eligible for pharmacokinetic analysis (eight in each cohort). For moderate and severe renal impairment versus normal renal function, GMR estimates were: clearance normalized to body surface area (CL/BSA) 0.95 (90% CI 0.80–1.13) and 0.89 (0.61–1.32); area under the curve normalized to dose (AUC/dose) 1.06 (0.88–1.27) and 1.14 (0.76–1.71); and F (U) 0.99 (0.94–1.04) and 0.97 (0.87–1.09), respectively. Estimated slopes of linear regression of log parameters versus log CrCL (renal impairment) were: CL/BSA 0.06 (−0.15 to 0.28); AUC/dose −0.07 (−0.30 to 0.16); and F (U) 0.02 (−0.05 to 0.08). Cabazitaxel safety profile was consistent with previous reports. CONCLUSIONS: Renal impairment had no clinically meaningful effect on cabazitaxel pharmacokinetics. Springer Berlin Heidelberg 2016-10-27 2016 /pmc/articles/PMC5114328/ /pubmed/27796539 http://dx.doi.org/10.1007/s00280-016-3175-7 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Article Azaro, Analía Rodón, Jordi Machiels, Jean-Pascal Rottey, Sylvie Damian, Silvia Baird, Richard Garcia-Corbacho, Javier Mathijssen, Ron H. J. Clot, Pierre-François Wack, Claudine Shen, Liji de Jonge, Maja J. A. A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function |
title | A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function |
title_full | A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function |
title_fullStr | A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function |
title_full_unstemmed | A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function |
title_short | A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function |
title_sort | phase i pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114328/ https://www.ncbi.nlm.nih.gov/pubmed/27796539 http://dx.doi.org/10.1007/s00280-016-3175-7 |
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