ORAL SDZ PSC 833 AND INTRAVENOUS PACLITAXEL IN ADVANCE CANCER

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The development of drug resistance to antineoplastic drugs is a tremendous obstacle to effective treatment of human malignancies. The problem of drug resistance is compounded by the emergence of tumors cross-resistant to multiple chemotherapeutic agents related in structure and function to the original selective agent. This phenomenon, termed multidrug resistance, may be caused by a protein, P-glycoprotein, which acts as an ATP-dependent efflux pump reducing the intracellular accumulation of certain antineoplastic agents. Because of the potential importance of P-glycoprotein in clinical drug resistance, many investigators have focused on pharmacologic reversal of this phenomenon. One of the pharmacologic agents able to reverse drug resistance in the laboratory is the cyclosporine derivative SDZ PSC 833. This study proposes to conduct a Phase I trial to determine the maximum tolerated dose of oral PSC 833 that can be given in combination with paclitaxel for patients with refractory malignancies and from malignancies for which there is no standard treatments.