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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Adult, Aged, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab, Brain Neoplasms, Clinical Trials, Phase II as Topic, Drug Administration Schedule, Electromyography, Female, Glioblastoma, Humans, Male, Middle Aged, Myasthenia Gravis, Neuromuscular Diseases, Neuromuscular Junction, Piperazines, Protein Kinase Inhibitors, Protein-Tyrosine Kinases, Quinazolines, Syndrome.
user
Does neuromuscular junction toxicity with tandutinib induce a myasthenic-like syndrome? Context: 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. 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). 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.
assistant
These observations suggest that tandutinib is toxic to the neuromuscular junction, possibly by reversibly binding to a molecule on the postsynaptic acetylcholine receptor complex. Final Decision: yes