Angiogenesis, the sprouting of capillaries from pre-existing vessels, is an essential event in many physiologic processes such as reproduction, development and wound healing. Angiogenesis inhibition has become a potential anti-tumor treatment strategy, as avascular tumors would be expected to be incapable of growth and have little metastatic potential. However, tumor regression in pre-clinical models in response to angiogenesis inhibitors is variable, depending on a host of factors, including the biological characteristics of the specific tumor, pharmacodynamic and pharmacokinetic responses, and the type of model system used. Since complete tumor regressions are rare in these model systems, it appears inhibition of angiogenesis alone may be insufficient for tumor remission. Therefore, combining angiogenesis inhibitors with other chemotherapeutic agents may have greater efficacy at tumor inhibition. MSI-1256F inhibits growth of solid tumors by inhibiting the development of a blood supply to the tumor without direct cytotoxicity to tumor cells. This effect appears to be mediated by the blockade of the stimulation of endothelial cells by any of a multiple of mitogens, apparently by modulation of endothelial cell pH, without obvious effect on quiescent endothelial cells or alteration of VEGF production by tumor cells. Therefore, MSI-1256F for injection is considered well suited for targeted therapy of tumors and other diseases characterized by neovascularization. This Phase IIA clinical trial is being performed to determine the safety and response rates of MSI-1256F for injection as a continuous intravenous infusion in combination with carboplatin and paclitaxel in patients with Stage IIIB (pleural effusion) and Stage IV non-small cell lung cancer.
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