A Preclinical and Clinical Study of Lithium in Low-Grade Neuroendocrine Tumors

2011 
Background. Low-grade neuroendocrine tumors (NETs) respond poorly to chemotherapy; effective, less toxic therapies are needed. Glycogen synthase kinase (GSK)-3 has been shown to regulate growth and hormone production in NETs. Use of lithium chloride in murine models suppressed carcinoid cell growth, reduced GSK-3 levels, and reduced expression of chromogranin A. This study assessed the efficacy of lithium chloride in patients with NETs. Design. Eligible patients had low-grade NETs. A single-arm, open-label phase II design was used. Lithium was dosed at 300 mg orally three times daily, titrated to serum levels of 0.8–1.0 mmol/L. The primary endpoint was objective tumor response by the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included overall survival, progression-free survival, GSK-3 phosphorylation, and toxicity. Results. Fifteen patients were enrolled between Octo
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