Cytokines, GM-CSF and IFNγ administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin

Apte, Sachin M.; Vadhan‐Raj, Saroj; Cohen, Lorenzo; Bassett, Roland L.; Gordon, Ilyssa O.; Levenback, Charles; Ramírez, Pedro T.; Gallardo, Stacie T; Patenia, Rebecca; Garcia, Michael; Iyer, Revathy B.; Freedman, Ralph S.

doi:10.1186/1479-5876-4-16

Cited by 10 publications

(8 citation statements)

References 46 publications

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“…Direct monocyte mediated cytotoxicity and ADCC activity was detected before and during the cytokine treatment, but there was no significant enhancement after GM-CSF or rIFN-γ1b. These findings are consistent with our previous report that the proportion of low affinity receptor CD16+ MO/MA, which mediate direct cytotoxicity as well as ADCC, are not increased following GM-CSF treatment [27]. However, the expansion of MO, which includes CD16+ ADCC effector cells, on day 9 of each cycle could suggest that day 9 of the carboplatin/GM-CSF regimen might be an appropriate time to include suitable human chimerized anti-tumor cell monoclonal antibodies, that are able to both target tumor cells in-vivo and provide selective binding to CD16+ effector cells.…”

Section: Discussionsupporting

confidence: 93%

“…Patients developing hypersensitivity were excluded from this analysis because of steroid usage. All values are reported for day 9 of each cycle, based on preliminary results showing maximum increase in MO after GM-CSF at this timepoint [27]. Although, there was mild variability between cycles, the median WBC, neutrophil and monocyte counts peaked at cycle 1 and remained elevated above baseline levels for all 6 cycles.…”

Section: Resultsmentioning

confidence: 99%

“…Purified monocytes were tested for their capacity to kill tumor cells both with and without an antibody capable of mediating ADCC using a previously described 3H-TdR release assay [26, 27]. The antibody construct employed in this assay was obtained from Macrogenics, Rockville, MD [28] and targets the HER2/neu antigen which is highly expressed on SKOV3 tumor cells.…”

Section: Methodsmentioning

confidence: 99%

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A phase II study of GM-CSF and rIFN-γ1b plus carboplatin for the treatment of recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer

Schmeler¹,

Vadhan‐Raj²,

Ramírez³

et al. 2009

Gynecologic Oncology

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Objective To evaluate the efficacy and toxicity of carboplatin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant interferon gamma 1b (rIFN-γ1b) in women with recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer. Methods In this phase II study, patients with recurrent, platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer were treated with subcutaneous GM-CSF and rIFN-γ1b before and after intravenous carboplatin until disease progression or unacceptable toxicity. All patients had measurable disease and a chemotherapy-free interval ≥6 months. Response was determined using RECIST criteria and CA 125 levels. Results Between 2003 and 2007, 59 patients received a median of 6 cycles of therapy (range, 1 to 13 cycles). Median age at enrollment was 61 years (range, 35 to 79 years). Median time to progression prior to enrollment was 11 months (range, 6 to 58 months). Of 54 patients evaluable for response, 9 (17%) had a complete response, 21 (39%) had a partial response, and 24 (44%) had progressive disease. The overall response rate was 56% (95% CI: 41% to 69%). With a median follow-up of 6.4 months, median time to progression was 6 months. Myeloid derived cells and platelets increased on day 9 of each chemotherapy cycle. The most common adverse effects were bone marrow suppression, carboplatin hypersensitivity, and fatigue. Responders reported improved quality of life. Conclusion This pre and post-carboplatin cytokine regimen resulted in a reasonable response and a hematologic profile that could invite further evaluation of its components in the treatment of patients with ovarian cancer.

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A phase II study of GM-CSF and rIFN-γ1b plus carboplatin for the treatment of recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer

Schmeler¹,

Vadhan‐Raj²,

Ramírez³

et al. 2009

Gynecologic Oncology

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“…Blood myeloid cells activated monocytes increased but without clear effects on antibody dependent cellular cytotoxicity [78] .…”

Section: Treatmentmentioning

confidence: 99%

Immunotherapy for Ovarian Cancer

Drerup

Liu

Padrón

et al. 2015

Curr. Treat. Options in Oncol.

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“…This cytokine has been linked to tumor growth, invasiveness, and metastatic potential in several cancers [110–112]. Similar to RAGE and its ligands, IL-1β and its receptor are expressed by various cell types within tumor microenvironment.…”

Section: Il-1β and Rage In Acute And Chronic Inflammatory And Metabolic Resmentioning

confidence: 99%

Il-1β, Rage and Fabp4: Targeting the Dynamic Trio in Metabolic Inflammation and Related Pathologies

Hardaway

Podgorski

2013

Future Med. Chem.

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Within the past decade, inflammatory and lipid mediators, such as IL-1β, FABP4 and RAGE, have emerged as important contributors to metabolic dysfunction. As growing experimental and clinical evidence continues to tie obesity-induced chronic inflammation with dysregulated lipid, insulin signaling and related pathologies, IL-1β, FABP4 and RAGE each are being independently implicated as culprits in these events. There are also convincing data that molecular pathways driven by these molecules are interconnected in exacerbating metabolic consequences of obesity. This article highlights the roles of IL-1β, FABP4 and RAGE in normal physiology as well as focusing specifically on their contribution to inflammation, insulin resistance, atherosclerosis, Type 2 diabetes and cancer. Studies implicating the interconnection between these pathways, current and emerging therapeutics, and their use as potential biomarkers are also discussed. Evidence of impact of IL-1β, FABP4 and RAGE pathways on severity of metabolic dysfunction underlines the strong links between inflammatory events, lipid metabolism and insulin regulation, and offers new intriguing approaches for future therapies of obesity-driven pathologies.

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Cytokines, GM-CSF and IFNγ administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin

Cited by 10 publications

References 46 publications

A phase II study of GM-CSF and rIFN-γ1b plus carboplatin for the treatment of recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer

A phase II study of GM-CSF and rIFN-γ1b plus carboplatin for the treatment of recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer

Immunotherapy for Ovarian Cancer

Il-1β, Rage and Fabp4: Targeting the Dynamic Trio in Metabolic Inflammation and Related Pathologies

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