This Program Project Grant evaluates the role of dose-intensification in the treatment of breast and ovarian cancer. We propose to use high dose combination alkylating agents and bone marrow support in the treatment of early metastatic breast cancer following induction chemotherapy with adriamycin and to use high dose chemotherapy and bone marrow support in high risk Stage II Breast cancer involving 10 or more lymph nodes and high dose systemic cyclophosphamide and thiotepa with bone marrow support and to perform phase I and phase II trials of high dose therapy and autologous bone marrow support in ovarian cancer. Using multiple monoclonal antibodies, we will monitor bone marrow for involvement with malignant breast cancer cells and develop immunopharmacologic methods for removing the malignant contamination. Two projects will attempt to ameliorate the toxicity of high dose chemotherapy. We will extend our initial observations using recombinant granulocyte macrophage colony-stimulating-factor (rHuGM-CSF) in shortening the period of myelosuppression following high dose therapy and autologous bone marrow support by performing a randomized, comparative trial. We will perform investigations to understand the mechanism underlying refractory and dysfunctional thrombocytopenia and evaluate the therapeutic approaches. The performance of these projects is supported by three core projects, involving cryopreservation, statistics and administration.
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