Madhusudan S et al. (2004) A phase II study of Etanercept (Enbrel), a tumor necrosis factor α inhibitor in patients with metastatic breast cancer. Clin Cancer Res 10: 6528–6534

Etanercept, originally developed for the treatment of rheumatoid arthritis, is a recombinant human soluble form of the p75 tumor necrosis factor-α (TNF-α) receptor, which inhibits binding of TNF-α to its cell surface receptor. The drug is also being investigated for its potential antitumor effect and results of a phase II study in metastatic breast cancer have recently been published.

Authors Madhusudan et al. carried out an open-label study in 16 women with advanced disease, in whom conventional therapy had failed. The patients received 25 mg doses of etanercept twice weekly by subcutaneous injection, for a median duration of 8.1 weeks.

The drug was well-tolerated; the most common adverse events were fatigue and injection site reactions such as rash and swelling. A significant increase in plasma levels of TNF-α indicated biological response to therapy in all patients. Additionally, a cytokine release assay showed decreased levels of interleukin-6 and Human monocyte chemoattractant protein-1 in peripheral blood samples in response to phytohemagglutinin, suggesting that downstream TNF-α-associated pathways were affected by the drug. Although no partial or complete responses were seen at this dose level, one patient achieved temporary disease stabilization after 12 weeks' therapy.

In summary, the study demonstrates the safety and biological activity of TNF-α blockade with etanercept in patients with metastatic breast cancer. Further studies will focus on different dosing schedules and combination with other therapies.