This program project grant application applies for continued funding for PPG CA-47741 for studies of high dose chemotherapy in autologous bone marrow support in the treatment of breast and ovarian cancer. The program consists of four projects and three core activities which are highly interrelated, dependent and interactive. In Project IA we propose to (1) complete the prospective randomized, comparative trials in Stage IV and Stage Il breast cancer begun as funded under the first application and (2) extend the use of high dose chemotherapy and autologous bone marrow support in three ways: (a) to apply high dose therapy to patients with primary breast cancer involving four to nine axillary nodes and (b) to patients with bone only disease in a randomized comparative trial; (c) to explore the use of a second high-dose chemotherapy regimen used in tandem. In Project lB, we evaluate the role of high-dose chemotherapy for ovarian cancer in clinical trials progressing from advanced disease to patients with disease remaining at second look surgery and through basic research targeted at the enhancement of the efficacy of alkylating agents. In Project II, we investigate the detection of malignant contamination of the bone marrow and peripheral blood with neoplastic cells using immunologic methods and utilize pharmacologic and immunologic methods to remove these malignant cells from the marrow. In Project IIIA, we propose studies of new combination of cytokines and schedule to extend our observations of CSF primed peripheral blood progenitor cells in patients with breast cancer undergoing high dose chemotherapy and will use ex vivo expansion of stem-cell enriched progenitors with emly acting cytokines to provide cells for support after high-dose therapy and to study in detail the distribution of cytokines and their receptors. The program project is supported by cryopreservation, statistical and administrative cores.
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