Clinical Medicine Reviews in Oncology

Cytokine therapy provides inadequate disease control and poor survival outcomes for patients with metastatic renal cell carcinoma (mRCC). Refined understanding of RCC biology identified molecular targets for the application of novel inhibitors. The monoclonal anti-VEGF antibody, bevacizumab, demonstrated efficacy and safety in phase II testing in patients with cytokine-refractory advanced RCC. The combination of bevacizumab and interferon significantly improved response rate and progression-free survival in two randomized phase III trials (AVOREN and CALGB 90206). The toxicity profile of the combination relates largely to that known to be associated with interferon. The contribution of Interferon to the combination's overall efficacy has been questioned. Because FDA approval of bevacizumab plus interferon did not specify the line of therapy, the place of the combination among other therapies (including tyrosine kinase and mTOR inhibitors) is the subject of debate. Trials of combinations of bevacizumab and other targeted agents (eg, erlotinib, temsirolimus) have produced unacceptable toxicity. There are ongoing trials designed to investigate the efficacy of bevacizumab monotherapy and bevacizumab in combination with attenuated dose of interferon or in combination with mechanistically different targeted agents.