99-Technetium Sestamibi Scanning to Predict the Efficacy of Estramustine Phosphate in Overcoming Paclitaxel Resistance in Patients With Advanced Breast Cancer
Abstract
This research investigates the ability of 99-Technetium Sestamibi (Tc-99-SM) to serve as a non-invasive means or 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 MDR, 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 are therefore in the process of rewriting the clinical protocol to reflect the use of ZD1839 as the MDR reversing agent in the study and submitting the revisions for IRB approval.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADA403456
Entities
People
- Matthew D. Volm
Organizations
- New York University