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Conference Paper: Phase I study of Pazopanib (PAZ) in Hepatocellular Carcinoma (HCC): evaluation of clinical activity, Pharmacokinetics (PK), and Dynamic Contrast Enhanced MRI (DCE-MRI)

TitlePhase I study of Pazopanib (PAZ) in Hepatocellular Carcinoma (HCC): evaluation of clinical activity, Pharmacokinetics (PK), and Dynamic Contrast Enhanced MRI (DCE-MRI)
Authors
Issue Date2009
PublisherElsevier BV. The Journal's web site is located at www.ejcancer.info/supplements
Citation
The 34th ESMO Multidisciplinary Congress (Joint ECCO 2015), Berlin, Germany, 20–24 September 2009. In European Journal of Cancer Supplements, 2009, v. 7 n. 2, p. 122, abstract no. 1206 How to Cite?
AbstractBackground: HCC is a highly vascular tumor with increased levels of VEGF and VEGFR. PAZ is an oral angiogenesis inhibitor targeting VEGFR, PDGFR, & c-Kit. A correlation between a trough plasma PAZ concentration (C24) of 15 mg/ml and markers of pharmacodynamic activity has been demonstrated in previous studies. DCE-MRI is a noninvasive imaging technique that can provide indices related to blood flow & vascular permeability. A Phase I study was conducted to determine the MTD as well as evaluate safety, PK, DCE-MRI changes, & clinical activity of PAZ in pts with locally unresectable or advanced HCC. Methods: Eligibility criteria included HCC with at least 1 target lesion, recovery from prior therapy, PS 0 or 1, Child-Pugh A, & adequate organ function. PAZ was escalated from 200 to 800 mg QD. DCE-MRI was performed to determine Ktrans (contrast transfer coefficient) & IAUC60 (initial area under the contrast enhancement curve), at baseline & Day 22. PAZ PK, including C24, was determined on Day 15 of Cycle 1. Median C24 was >15 mg/mL at all doses evaluated. Median changes in Ktrans & IAUC were negative in all dose groups with the greatest median decline at 800 mg. Decreases in IAUC60 were correlated with Cmax and trough concentration. At the MTD of 600 mg QD, median decline from baseline in imaging markers was ~40%; 67% of pts achieved C24 15 ug/mL. Of 10 pts who received 600 mg QD for the largest number of days on study, 7 demonstrated clinical benefit (6 with SD 4 mo & 1 with confirmed PR). The 2 pts with confirmed PRs (1 each at 600 mg & 800 mg QD) both achieved C24 >25 ug/mL. 1 pt with PR & imaging data achieved >60% declines in Ktrans & IAUC relative to baseline. Conclusions: In pts with HCC, the recommended Phase II dose for PAZ of 600 mg QD achieved target trough concentrations associated with clinical benefit & demonstrated meaningful changes in imaging markers.
Persistent Identifierhttp://hdl.handle.net/10722/186806
ISSN
2010 Impact Factor: 9.386
2015 SCImago Journal Rankings: 0.217

 

DC FieldValueLanguage
dc.contributor.authorYau, TCCen_US
dc.contributor.authorChen, Pen_US
dc.contributor.authorCurtis, Cen_US
dc.contributor.authorMurphy, Pen_US
dc.contributor.authorParker, Gen_US
dc.contributor.authorSuttle, Aen_US
dc.contributor.authorArumugham, Ten_US
dc.contributor.authorHodge, Jen_US
dc.contributor.authorDar, Men_US
dc.contributor.authorPoon, RTPen_US
dc.date.accessioned2013-08-20T12:21:06Z-
dc.date.available2013-08-20T12:21:06Z-
dc.date.issued2009en_US
dc.identifier.citationThe 34th ESMO Multidisciplinary Congress (Joint ECCO 2015), Berlin, Germany, 20–24 September 2009. In European Journal of Cancer Supplements, 2009, v. 7 n. 2, p. 122, abstract no. 1206en_US
dc.identifier.issn1359-6349-
dc.identifier.urihttp://hdl.handle.net/10722/186806-
dc.description.abstractBackground: HCC is a highly vascular tumor with increased levels of VEGF and VEGFR. PAZ is an oral angiogenesis inhibitor targeting VEGFR, PDGFR, & c-Kit. A correlation between a trough plasma PAZ concentration (C24) of 15 mg/ml and markers of pharmacodynamic activity has been demonstrated in previous studies. DCE-MRI is a noninvasive imaging technique that can provide indices related to blood flow & vascular permeability. A Phase I study was conducted to determine the MTD as well as evaluate safety, PK, DCE-MRI changes, & clinical activity of PAZ in pts with locally unresectable or advanced HCC. Methods: Eligibility criteria included HCC with at least 1 target lesion, recovery from prior therapy, PS 0 or 1, Child-Pugh A, & adequate organ function. PAZ was escalated from 200 to 800 mg QD. DCE-MRI was performed to determine Ktrans (contrast transfer coefficient) & IAUC60 (initial area under the contrast enhancement curve), at baseline & Day 22. PAZ PK, including C24, was determined on Day 15 of Cycle 1. Median C24 was >15 mg/mL at all doses evaluated. Median changes in Ktrans & IAUC were negative in all dose groups with the greatest median decline at 800 mg. Decreases in IAUC60 were correlated with Cmax and trough concentration. At the MTD of 600 mg QD, median decline from baseline in imaging markers was ~40%; 67% of pts achieved C24 15 ug/mL. Of 10 pts who received 600 mg QD for the largest number of days on study, 7 demonstrated clinical benefit (6 with SD 4 mo & 1 with confirmed PR). The 2 pts with confirmed PRs (1 each at 600 mg & 800 mg QD) both achieved C24 >25 ug/mL. 1 pt with PR & imaging data achieved >60% declines in Ktrans & IAUC relative to baseline. Conclusions: In pts with HCC, the recommended Phase II dose for PAZ of 600 mg QD achieved target trough concentrations associated with clinical benefit & demonstrated meaningful changes in imaging markers.-
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at www.ejcancer.info/supplements-
dc.relation.ispartofEuropean Journal of Cancer Supplementsen_US
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in European Journal of Cancer Supplements. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in In European Journal of Cancer Supplements, 2009, v. 7 n. 2, p. 122, abstract no. 1206 DOI# 10.1016/S1359-6349(09)70418-5-
dc.titlePhase I study of Pazopanib (PAZ) in Hepatocellular Carcinoma (HCC): evaluation of clinical activity, Pharmacokinetics (PK), and Dynamic Contrast Enhanced MRI (DCE-MRI)en_US
dc.typeConference_Paperen_US
dc.identifier.emailYau, TCC: tyaucc@hku.hken_US
dc.identifier.emailPoon, RTP: poontp@hku.hken_US
dc.identifier.authorityYau, TCC=rp01466en_US
dc.identifier.authorityPoon, RTP=rp00446en_US
dc.identifier.doi10.1016/S1359-6349(09)70418-5-
dc.identifier.hkuros217128en_US
dc.identifier.volume7-
dc.identifier.issue2-
dc.identifier.spage122, abstract no. 1206en_US
dc.identifier.epage122, abstract no. 1206en_US
dc.publisher.placeUnited Kingdom-

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