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Study of Etanercept, a Tumor Necrosis Factor-Alpha Inhibitor, in Recurrent Ovarian Cancer

From Cancer Research UK Medical Oncology Unit, University of Oxford, Churchill Hospital, Oxford; and Cancer Research UK Translational Oncology Laboratory, Barts and the London, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London, United Kingdom

Address reprint requests to Trivadi S. Ganesan, MD, PhD, FRCP, Cancer Research UK Cancer Centre, Churchill Hospital, OX3 7LJ Oxford, United Kingdom; e-mail: ganesan{at}cancer.org.uk

PURPOSE: Convincing data support the link between inflammation and ovarian cancer. Tumor necrosis factor-alpha (TNF-), 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- 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 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.

Supported by Cancer Research UK.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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