| Neuromuscular junction toxicity with tandutinib induces a myasthenic-like syndrome. | |
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MedLine Citation:
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PMID: 21242491 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Tandutinib (MLN 518, Millennium Pharmaceuticals, Cambridge, MA) is an orally active multitargeted tyrosine kinase inhibitor that is currently under evaluation for the treatment of glioblastoma and has been used in the treatment of leukemia. In prior clinical and animal studies, a dose-dependent muscular weakness has been observed with this drug, though the etiology of the weakness has not been defined. METHODS: Standard neurophysiologic techniques, including repetitive nerve stimulation, needle EMG, and single-fiber EMG, were used to evaluate patients who developed weakness while being treated with tandutinib and bevacizumab (Avastin, Genentech, South San Francisco, CA) for glioblastoma (NCT00667394). RESULTS: Six patients were observed to develop a reversible weakness that correlated with the administration of the tandutinib. The onset of weakness after starting tandutinib occurred within 3 to 112 days and in less than 15 days in 3 patients. Electrophysiologic studies showed that all patients developed abnormal repetitive nerve stimulation studies. Four patients had short duration motor unit potentials. Two of these patients also had abnormal single-fiber EMG, as did a third patient who did not have standard needle EMG. The clinical and electrophysiologic abnormalities improved with the termination or reduction in the dose of tandutinib. CONCLUSION: These observations suggest that tandutinib is toxic to the neuromuscular junction, possibly by reversibly binding to a molecule on the postsynaptic acetylcholine receptor complex. Classification of evidence: This study provides Class III evidence that tandutinib 500 mg twice daily induces reversible muscle weakness and electrophysiologic changes consistent with neuromuscular junction dysfunction. |
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Authors:
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T J Lehky; F M Iwamoto; T N Kreisl; M K Floeter; H A Fine |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural |
Journal Detail:
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Title: Neurology Volume: 76 ISSN: 1526-632X ISO Abbreviation: Neurology Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-18 Completed Date: 2011-02-14 Revised Date: 2012-01-18 |
Medline Journal Info:
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Nlm Unique ID: 0401060 Medline TA: Neurology Country: United States |
Other Details:
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Languages: eng Pagination: 236-41 Citation Subset: AIM; IM |
Affiliation:
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EMG Section, NINDS, NIH, 8900 Wisconsin Ave., Bethesda, MD 20892-1404, USA. lehkyt@ninds.nih.gov |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00667394 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Antibodies, Monoclonal / administration & dosage Antibodies, Monoclonal, Humanized Antineoplastic Combined Chemotherapy Protocols / adverse effects Brain Neoplasms / drug therapy Clinical Trials, Phase II as Topic Drug Administration Schedule Electromyography Female Glioblastoma / drug therapy Humans Male Middle Aged Myasthenia Gravis / chemically induced*, physiopathology Neuromuscular Diseases / chemically induced Neuromuscular Junction / drug effects*, physiopathology Piperazines / administration & dosage, adverse effects* Protein Kinase Inhibitors / administration & dosage, adverse effects* Protein-Tyrosine Kinases / antagonists & inhibitors* Quinazolines / administration & dosage, adverse effects* Syndrome |
| Chemical | |
Reg. No./Substance:
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0/4-(6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl)piperazine-1-carboxylic acid (4-isopropoxyphenyl)amide; 0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Piperazines; 0/Protein Kinase Inhibitors; 0/Quinazolines; 0/bevacizumab; EC 2.7.10.1/Protein-Tyrosine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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