PURPOSE: Convincing data support the link between inflammation and ovarian cancer. Tumor necrosis factor-alpha (TNF-alpha), a major mediator of inflammation, is chronically produced in the ovarian tumor microenvironment and may enhance tumor growth and invasion by inducing the secretion of cytokines, proangiogenic factors, and metalloproteinases. Etanercept is a recombinant human soluble p75 TNF receptor that binds to TNF-alpha and renders it biologically unavailable. In the current study, we sought to determine the toxicity, biologic activity, and therapeutic efficacy of etanercept in recurrent ovarian cancer. PATIENTS AND METHODS: We initiated a phase I-B, nonrandomized, open-label study in patients with recurrent ovarian cancer. Etanercept was administered subcutaneously at a dose of 25 mg twice weekly (cohort one) and 25 mg thrice weekly (cohort two) until disease progression. RESULTS: Thirty patients were recruited (cohort one, 17 patients; cohort two, 13 patients). Eighteen of the 30 patients (cohort one, 11 patients; cohort two, seven patients) completed > or = 12 weeks of treatment. Six patients achieved prolonged disease stabilization (cohort one, two patients [40 and 25 weeks]; cohort two, four patients [34, 24, 22, and 24 weeks]). A significant rise in immunoreactive TNF was seen in all patients (pretreatment compared with end of treatment). A phytohemagglutinin-stimulated whole-blood cytokine assay showed a significant fall in interleukin-6 (cohort one [11 of 17]) and CCL2 (cohort one [13 of 17]) levels. Common adverse effects were injection-site reactions and fatigue. CONCLUSION: We provide evidence for the biologic activity and safety of etanercept in recurrent ovarian cancer. Our data suggest possible clinical activity that must be confirmed in future studies.
PURPOSE: Convincing data support the link between inflammation and ovarian cancer. Tumor necrosis factor-alpha (TNF-alpha), a major mediator of inflammation, is chronically produced in the ovarian tumor microenvironment and may enhance tumor growth and invasion by inducing the secretion of cytokines, proangiogenic factors, and metalloproteinases. Etanercept is a recombinant human soluble p75TNF receptor that binds to TNF-alpha and renders it biologically unavailable. In the current study, we sought to determine the toxicity, biologic activity, and therapeutic efficacy of etanercept in recurrent ovarian cancer. PATIENTS AND METHODS: We initiated a phase I-B, nonrandomized, open-label study in patients with recurrent ovarian cancer. Etanercept was administered subcutaneously at a dose of 25 mg twice weekly (cohort one) and 25 mg thrice weekly (cohort two) until disease progression. RESULTS: Thirty patients were recruited (cohort one, 17 patients; cohort two, 13 patients). Eighteen of the 30 patients (cohort one, 11 patients; cohort two, seven patients) completed > or = 12 weeks of treatment. Six patients achieved prolonged disease stabilization (cohort one, two patients [40 and 25 weeks]; cohort two, four patients [34, 24, 22, and 24 weeks]). A significant rise in immunoreactive TNF was seen in all patients (pretreatment compared with end of treatment). A phytohemagglutinin-stimulated whole-blood cytokine assay showed a significant fall in interleukin-6 (cohort one [11 of 17]) and CCL2 (cohort one [13 of 17]) levels. Common adverse effects were injection-site reactions and fatigue. CONCLUSION: We provide evidence for the biologic activity and safety of etanercept in recurrent ovarian cancer. Our data suggest possible clinical activity that must be confirmed in future studies.
Authors: Christina Wu; Soledad A Fernandez; Tamara Criswell; Tarek A Chidiac; Denis Guttridge; Miguel Villalona-Calero; Tanios S Bekaii-Saab Journal: Pancreas Date: 2013-07 Impact factor: 3.327
Authors: Andrew H Miller; Sonia Ancoli-Israel; Julienne E Bower; Lucile Capuron; Michael R Irwin Journal: J Clin Oncol Date: 2008-02-20 Impact factor: 44.544