Abstract
BACKGROUND: Monocyte/macrophages (MO/MA), a polymorphic population of innate immune cells, have the potential to mediate antitumor effects, and may also contribute to protumor effects. A priming and post-chemotherapy schedule of the myeloid cell mobilizing and immune stimulatory growth factor, granulocyte monocyte stimulating factor (GM-CSF, Leukine) and the MO/MA activating cytokine recombinant interferon gamma 1b (rIFN-gamma1b, Actimmune) has been developed. The pre- and post-chemotherapy design is based upon known in vivo kinetics and immune modulatory effects of these molecules. Carboplatin (Paraplatin) was selected as the cornerstone of treatment of epithelial ovarian cancer (EOC). METHODS: We studied hematopoietic and immunologic effects of GM-CSF and rIFN-gamma1b before and after carboplatin in patients with recurrent EOC. Potentially chemotherapy-sensitive patients with recurrent measurable tumors received subcutaneous GM-CSF (starting at 400 mug/day) for 7 days plus subcutaneous rIFN-gamma1b (100 mug) on days 5 and 7, before and after intravenous carboplatin (area under the curve of 5). We performed standard hematologic assessment and monitored monocyte (MO), dendritic cell, major cell subset counts, and antibody-dependent cell-mediated cytotoxicity (ADCC) against a Her2neu+ tumor cell line, as well as selected plasma inflammatory cytokine, chemokine and growth factor levels. RESULTS: Our analysis comprised only the first 3 months of treatment in the initial 25 patients. Relative to pretreatment baseline values, white blood cell, neutrophil, MO, and eosinophil counts increased (P