Malignant cells have the ability to develop resistance to cytotoxic chemotherapy. Once such mechanism is through the development of resistance to several classes of chemotherapeutic agents, including the anthracyclines, taxanes, epipodophyllotoxins and vinca alkaloids. This resistance prototype is called the multidrug resistance phenotype (MDR). The resistance is conferred through the presence of a glycoprotein pump that serves to eliminate certain chemotherapeutic agents from the malignant cell. LY335979 is an agent that has been shown in in vitro cell culture models to inhibit the MDR pump, p-glycoprotein. This study is the first attempt to expose humans to LY335979 in its intravenous form and to characterize its toxicity and pharmacokinetic profile. This is a nonrandomized study of LY335979 and doxorubicin in patients with histologically or cytologically documented malignancy who have failed conventional therapy or whose disease is considered refractory to standard chemotherapeutic regimens or for which no standard chemo- therapy is available.
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