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dc.contributor.authorAzaro, Aen
dc.contributor.authorRodón, Jen
dc.contributor.authorMachiels, J-Pen
dc.contributor.authorRottey, Sen
dc.contributor.authorDamian, Sen
dc.contributor.authorBaird, Richarden
dc.contributor.authorGarcia-Corbacho, Jen
dc.contributor.authorMathijssen, RHJen
dc.contributor.authorClot, P-Fen
dc.contributor.authorWack, Cen
dc.contributor.authorShen, Len
dc.contributor.authorde Jonge, MJAen
dc.date.accessioned2016-12-19T15:14:12Z
dc.date.available2016-12-19T15:14:12Z
dc.date.issued2016-12-01en
dc.identifier.issn0344-5704
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/261646
dc.description.abstract$\textbf{PURPOSE}$ 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. $\textbf{METHODS}$ 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$^{2}$). $\textbf{RESULTS}$ 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. $\textbf{CONCLUSIONS}$ Renal impairment had no clinically meaningful effect on cabazitaxel pharmacokinetics.
dc.description.sponsorshipThis study was supported by Sanofi. Javier Garcia-Corbacho acknowledges clinical fellowship support from SEOM. Experimental Cancer Medicine Centre (ECMC) and NIHR Biomedical Research Centre (BRC) funding is also acknowledged for the Cambridge Cancer Centre.
dc.languageengen
dc.language.isoenen
dc.publisherSpringer
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectcabazitaxelen
dc.subjectrenal impairmenten
dc.subjectpharmacokineticsen
dc.subjectphase Ien
dc.subjectadvanced solid tumorsen
dc.titleA phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal functionen
dc.typeArticle
prism.endingPage1197
prism.issueIdentifier6en
prism.publicationDate2016en
prism.publicationNameCancer Chemotherapy and Pharmacologyen
prism.startingPage1185
prism.volume78en
dc.identifier.doi10.17863/CAM.6856
dcterms.dateAccepted2016-10-12en
rioxxterms.versionofrecord10.1007/s00280-016-3175-7en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-12-01en
dc.contributor.orcidBaird, Richard [0000-0001-7071-6483]
dc.identifier.eissn1432-0843
rioxxterms.typeJournal Article/Reviewen
cam.issuedOnline2016-10-27en
cam.orpheus.successThu Jan 30 12:56:53 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
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