My research interests span several areas that link my clinical practice with research initiatives. My research activity focuses on developing new, improved treatment options for persons with breast cancer, lung cancer, HIV malignancies and other malignancies and spans Phase I, II, and III clinical trials in single centre and multicentre cooperative arenas, as well as research to understand the character of cancer and its effect on patients.
The development of new and effective therapeutic options for patients with malignancies requires a coordination of scientists and clinicians to proceed with a rationale and practical approach. At the BCCA our investigational drug program tries to mix laboratory science with clinical input to develop new strategies for anticancer therapy, using our expertise in drug development and applied research with our clinical facilities. This allows clinical input into the design of drugs and their initial preclinical trials and allow basic science input into our Phase 1 and Phase 2 clinical trials. We have successfully taken liposomal vincristine through its intial preclinical development, into a IND approved by the Health Protection Branch and through one Phase I and two Phase II clinical trials. I am also involved in the development of another standard cytotoxic, anhydrovinblastine, which has been through preclinical testing and should enter clinical Phase 1 testing at the BCCA in l998. With other local companies we are exploring other options for anticancer therapy which may result in agents with novel mechanisms. This includes cationic fusion peptides which in the preclinical cell culture studies look active and promising, antisense strategies with bCL-2, ribosome technology against for example VEGF, modifiers of drug resistance, and other avenues of inhibiting cell growth. We will be testing many natural products which may be used in complementary medicine but may have potential if proven active in standard testing.
I am interested in how we are going to develop new agents and what endpoints we will need to evaluate these new biological modifiers. Our current preclinical and clinical assessments are based on standard cytotoxics and cell kill. New agents, including antiangiogenesis drugs, tyrosine kinase inhibitors and antisense therapy, may not be evaluable by our existing formulae and will need creative trial design. To further explore this area, I am organizing a workshop at the NCI/EORTC Symposium on New Drugs in June l998 with plans to expand this area of research.I have been active in Phase II and III clinical trials of new drugs in breast and lung cancer and Kaposi's sarcoma. In particular I was active in studies of the role of the taxanes in these malignancies. Although standard cytotoxics do have a role in treatment and new drugs should be assessed, the experience with these studies suggests that other agents must be explored. The idea of a cascade or series of interventions against the cell with an understanding of its genetic makeup is an area which needs to be studied in the laboratory and initiated in the clinic if we are going to make further gains.