Research Interests: Clinical cancer, drug development, clinical pharmacology in topoisomerase-1 inhibitors.

Early clinical drug development in cancer chemotherapy requires understanding the basic drug behavior in the human. This coupled with toxicity and activity in preclinical systems sets a basis for the earliest development in patients. We are interested in developing new combinations of chemotherapy as well as bringing new drugs into the clinic. Better understanding of the mechanism of drug action allows us to correlate these properties with clinical anti-tumor activity. Recent work that we have performed at NYU Medical Center include anthracycline drug development with newer analogs, cardioprotection and platinum analogs.

Most of our recent work has been in the area of topoisomerase-1 inhibitor development. This new class of compounds acts on a specific enzyme found in the nucleus that is essential for DNA application. When these drugs are given, cells cannot replicate and they die. Additional testing which we have performed has shown a 2 to 3 fold increased level of these enzymes in tumor tissues compared to corresponding normal tissues in specimens removed from patients at the time of surgery. We have performed phase I studies with the particular interest of giving these topoisomerase-1 inhibitors over prolonged time periods (up to 21 days of infusion therapy). These schedules have found great success and are currently in phase II development for both topotecan and 9-aminocamptothecin. Studies on tumor levels of the target enzyme topoisomerase-1 and depletion lymphocytes during therapy with topoisomerase-1 inhibitors has led us to important conclusions regarding the mechanisms of action of these new agents.

Representative