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Title of Journal: Cancer Chemother Pharmacol

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Abbravation: Cancer Chemotherapy and Pharmacology

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Springer-Verlag

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DOI

10.1007/bf00335433

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1432-0843

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A multihistology trial of fostamatinib in patient

Authors: Sook Ryun Park Giovanna Speranza Richard Piekarz John J Wright Robert J Kinders Lihua Wang Thomas Pfister Jane B Trepel MinJung Lee Sylvia Alarcon Seth M Steinberg Jerry Collins James H Doroshow Shivaani Kummar
Publish Date: 2013/02/13
Volume: 71, Issue: 4, Pages: 981-990
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Abstract

A multicohort phase II study of fostamatinib an oral multikinase inhibitor was conducted to determine the response rate in patients with advanced colorectal CRC thyroid nonsmall cell lung head and neck and renal cell carcinomas and pheochromocytomasA total of 37 patients 22 CRC median of 4 prior therapies were enrolled Due to toxicities in four of the first five patients the study was amended to incorporate a dose escalation phase for each histology The maximumtolerated dose was established at 50 mg BID in CRC but was not established for the other cancers Common grade 3/4 toxicities included transaminitis hyperbilirubinemia and hypertension Pharmacokinetic profile was similar to previous reports Seventythree percent of CRC patients had liver involvement and 91  had prior antiangiogenic therapy Patients with abnormal liver tests at baseline were more likely to experience grade ≥2 hepatotoxicity than those with normal tests 44 vs 0  No responses were observed disease stabilization rate was 27  in CRC Reduction in CECs following treatment was associated with a better disease stabilization rate 75 vs 0  in CRCFostamatinib had limited antitumor activity in this first clinical trial in patients with advanced refractory solid tumors reduction in CECs and CEPs was indicative of antiangiogenic effects Abnormal liver testing at baseline appeared to influence drug tolerabilityThis project has been funded in whole or in part with federal funds from the National cancer institute National institutes of health under contract no HHSN261200800001E The content of this publication does not necessarily reflect the views or policies of the department of health and human services nor does mention of trade names commercial products or organizations imply endorsement by the US government

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