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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2003-12-5
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pubmed:abstractText |
Obtaining direct and rapid proof of molecular activity in early clinical trials is critical for optimal clinical development of novel targeted therapies. SU11248 is an oral multitargeted kinase inhibitor with selectivity for fms-related tyrosine kinase 3/Flk2 (FLT3), platelet-derived growth factor receptor alpha/beta, vascular endothelial growth factor receptor 1/2, and KIT receptor tyrosine kinases. FLT3 is a promising candidate for targeted therapy in acute myeloid leukemia (AML), because activating mutations occur in up to 30% of patients. We conducted an innovative single-dose clinical study with a primary objective to demonstrate inhibition of FLT3 phosphorylation by SU11248 in AML. Experimental Design: Twenty-nine AML patients each received a single dose of SU11248, escalated from 50 to 350 mg, in increments of 50 mg and cohorts of three to six patients. FLT3 phosphorylation and plasma pharmacokinetics were evaluated at seven time points over 48 h after SU11248 administration, and FLT3 genotype was determined. Study drug-related adverse events occurred in 31% of patients, mainly grade 1 or 2 diarrhea and nausea, at higher dose levels.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1078-0432
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pubmed:author |
pubmed-author:BelloCarloC,
pubmed-author:BerdelWolfgang EWE,
pubmed-author:CherringtonJulie MJM,
pubmed-author:CooperMaureen AMA,
pubmed-author:FiedlerWalterW,
pubmed-author:ForanJames MJM,
pubmed-author:HeinrichMichael CMC,
pubmed-author:JacobsMarkM,
pubmed-author:KelseyStephenS,
pubmed-author:KimHeidiH,
pubmed-author:LouieSharianne GSG,
pubmed-author:ManningWilliam CWC,
pubmed-author:NicholasSusanS,
pubmed-author:O'FarrellAnne-MarieAM,
pubmed-author:PaquetteRon LRL,
pubmed-author:ScigallaPaulP,
pubmed-author:ServeHubertH,
pubmed-author:YuenHelene AHA
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5465-76
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14654525-Administration, Oral,
pubmed-meshheading:14654525-Adult,
pubmed-meshheading:14654525-Aged,
pubmed-meshheading:14654525-Blast Crisis,
pubmed-meshheading:14654525-Enzyme Inhibitors,
pubmed-meshheading:14654525-Female,
pubmed-meshheading:14654525-Genotype,
pubmed-meshheading:14654525-Humans,
pubmed-meshheading:14654525-Indoles,
pubmed-meshheading:14654525-Leukemia, Myeloid, Acute,
pubmed-meshheading:14654525-Male,
pubmed-meshheading:14654525-Metabolic Clearance Rate,
pubmed-meshheading:14654525-Middle Aged,
pubmed-meshheading:14654525-Mitogen-Activated Protein Kinases,
pubmed-meshheading:14654525-Phosphorylation,
pubmed-meshheading:14654525-Proto-Oncogene Proteins,
pubmed-meshheading:14654525-Pyrroles,
pubmed-meshheading:14654525-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:14654525-fms-Like Tyrosine Kinase 3
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pubmed:year |
2003
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pubmed:articleTitle |
An innovative phase I clinical study demonstrates inhibition of FLT3 phosphorylation by SU11248 in acute myeloid leukemia patients.
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pubmed:affiliation |
SUGEN Inc., South San Francisco, California, USA. marie@ceolas.org
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, U.S. Gov't, Non-P.H.S.,
Multicenter Study,
Clinical Trial, Phase I
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