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99-Technetium Sestamibi Scanning to Predict the Efficacy of Estramustine Phosphate in Overcoming Paclitaxel Resistance in Patients With Advanced Breast Cancer

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Annual rept. 1 Sep 2001-31 Aug 2002

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This research investigates the ability of 99-Technetium Sestamibi Tc-99-SM to serve as a non-invasive means of assessing the presence of clinically relevant drug resistance in patients with advanced breast cancer Tc-99-SM is a substrate of p-glycoprotein P-gp, the transmembrane drug efflux transporter involved in classic multi-drug resistance MDR We hypothesize that rapid clearance of Tc-99-SM correlates with the presence of functional multi-drug resistance and can be used to predict which patients will have tumors resistant to drugs that are MDR substrates We have demonstrated marked variability in the tumor clearance of Tc-99-SM among patients The second stage of our work is to conduct a clinical trial to determine whether changes in 99-Tc-SM clearance following the administration of an MDR inhibitor can predict effectiveness of the inhibitor in overcoming drug resistance We have met with difficulty in obtaining an MDR inhibitor appropriate for use in the study, as recent studies have cast doubt on the ability of estramustine to reverse MDP, and biricodar, our second choice, is no longer being manufactured Recently, however, compelling laboratory studies have shown that the agent ZD1839 Iressa is a highly potent inhibitor of P-gp and other drug efflux transporters likely to be significant mediators of drug resistance in breast cancer ZD1839 is expected to be an important anti-cancer agent in the coming decade, and using it to test our hypothesis in a clinical trial will provide valuable - information We have therefore rewritten the clinical protocol to reflect the use of ZD1839 as the MDR reversing agent and have received approval from our IRB for this study and are awaiting approval from the FDA and the DODs Human Subjects Research Review Board.

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  • Anatomy and Physiology
  • Medicine and Medical Research
  • Pharmacology

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