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- Title
Cytokines, GM-CSF and IFNγ administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin.
- Authors
Apte, Sachin M.; Vadhan-Raj, Saroj; Cohen, Lorenzo; Bassett, Roland L.; Gordon, Ilyssa O.; Levenback, Charles F.; Ramirez, Pedro T.; Gallardo, Stacie T.; Patenia, Rebecca S.; Garcia, Michael E.; Iyer, Revathy B.; Freedman, Ralph S.
- 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-γ1b, 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-γ1b before and after carboplatin in patients with recurrent EOC. Potentially chemotherapy-sensitive patients with recurrent measurable tumors received subcutaneous GM-CSF (starting at 400 μg/day) for 7 days plus subcutaneous rIFN-γ1b (100 μg) 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 ⩽ .001 for each); the proportion of platelets increased 9 days after the second (P ⩽ .002) and third (P ⩽ .04) carboplatin treatments; and the number of cells in the activated MO subsets CD14+HLA-DR+, CD14+CD64+, and CD14+CXCR3+ increased (P ⩽ .04 for each); plasma levels of the proangiogenic interleukins lα, 6, and 8 were lower (P ⩽ .03 for each); M-CSF, a product of activated MO/MA, was increased on day 9 (P ⩽ .007); and GM-CSF was increased in plasma after GM-CSF administration (P ⩽ .04). Quality of life measurements were reduced during the GM-CSF/IFN-γ1b cycle while recovering at pre-chemotherapy baseline for FACT-G scores only. Conclusion: A novel regimen of GM-CSF plus IFN-γ1b administered to 25 EOC patients receiving carboplatin increased myeloid cells, platelets and total activated MO populations during the initial 3 months; however, ADCC responses were not consistently enhanced during this period.
- Subjects
OVARIAN cancer; CYTOKINES; NATURAL immunity; MACROPHAGES; TUMOR treatment; DRUG therapy; NEUTROPHILS
- Publication
Journal of Translational Medicine, 2006, Vol 4, p16
- ISSN
1479-5876
- Publication type
Article
- DOI
10.1186/1479-5876-4-16