This is a study to assess the efficacy and safety of 3,4-diaminopyridine (DAP) in patients with Lambert-Eaton myasthenic syndrome (LEMS). LEMS is a rare disorder of neuromuscular transmission that produces weakness of varying severity and autonomic dysfunction. It is frequently associated with small cell lung cancer and results from an autoimmune reaction against the presynaptic nerve terminal. DAP is an orphan drug that has been used in other countries for over 20 years to treat patients with LEMS and other diseases with abnormal neuromuscular transmission, but which has not been approved for clinical use in this country. Treatments for LEMS include therapy for any underlying cancer, which frequently produces improvement in weakness as well; cholinesterase inhibitors, which usually produce only limited benefit; guanidine, which can produce severe side-effects; immunosuppression, which is usually only minimally or moderately effective; and plasmapheresis or high-dose immunoglobulin infusions, which produce only temporary improvement and are very expensive. Many patients with LEMS achieve marked improvement in symptoms and function with DAP. This study consists of a blinded, placebo-controlled phase to assess efficacy and a chronic open-label phase to assess safety of DAP in patients with LEMS. During the blinded phase, patients are hospitalized on the Clinical Research Unit for 10 days to observe therapeutic responses and potential adverse reactions to the study drug. Patients may also be hospitalized on the CRU when they return for 3 follow-up evaluations during the 6 month open-label phase of the study. 26 patients with LEMS will be treated under this study, which began July 1994. 15 patients have completed the study to date. Two patients died of lung cancer, two had no benefit from open-label DAP and one discontinued DAP when brain metastases were discovered. The other ten patients continue taking open-label DAP, with clinical benefit. There have been no adverse reactions to DAP in these patients other than mild paresthesias and no abnormalities on tests of cardiac, brain, renal, hepatic, hematopoietic and endocrine function. This study will continue until 26 patients have completed the protocol, which should be by July 1998.
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