Over the past year, the Medical Breast Cancer Section has significantly expanded its clinical trial treatment effort, increasing the number of clinical protocols and doubling patient accrual. 'ne clinical focus of the Medical Breast Cancer Section since 1988 has been four-fold: the development of 1) dose-intensive therapies in combination with hematopoietic growth factors; 2) new cytotoxic agents; 3) targeted therapies against tumor-associated antigens; and 4) the study of drug resistance markers in breast cancer. The major questions we have been interested in studying are: 1) Do dose-intensive cytotoxic regimens improve patient outcome (response rates, disease-free survival [DFS], overall survival [OS])?; 2) Do hematopoietic growth factors sufficiently ameliorate myelosuppression to enable the delivery of more dose-intensive therapy?; 3) What is the anti-tumor activity of intensive doses of new cytotoxic agents in combination with hematopoietic growth factors?; 4) How can the antitumor activity of radioimmunotherapy be enhanced?; and 5) Does cytotoxic chemotherapy change the baseline expression of the drug resistance markers P-glycoprotein and glutathione transferase pi (GSTpi) in primary breast cancer? The clinical trials addressing these questions are summarized below. Over the past year, we have completed our Phase II frontline dose intensity trial for metastatic breast cancer and three Phase I or II trials of new cytotoxic agents. We have initiated a second generation dose intensity trial with hematopoietic growth factors and have recently begun a Phase I study of taxol and the P-glycoprotein blocker, R-verapamil. In addition, a Phase I study of the monoclonal antibody CC-49 directed against the pancarcinoma antigen, TAG-72, radiolabeled with a novel Beta emitter Lutetim- 177 is underway. Lastly, we have completed the review process and will soon begin a pilot study of the feasibility of obtaining bone marrow engraftment with marrow and peripheral blood stem cell autografts that have been transduced with the neomycin resistance marker gene. This trial will be the forerunner to an upcoming study of marrow reconstitution with mdr-1- transduced marrow and peripheral blood stem cells in patients with metastatic breast cancer.
