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Genitourinary Cancer

Combination Systemic Therapy for Advanced Renal Cell Carcinoma

Department of Medicine, Royal Marsden Hospital, London, United Kingdom

Key Words. Renal cancer • Systemic therapy • mTOR • VEGF • Immunotherapy • Combination

Correspondence: James M.G. Larkin, M.A., M.R.C.P., Ph.D., Department of Medicine, Royal Marsden Hospital, London, SW3 6JJ, United Kingdom. Telephone: 44-207-808-2132; Fax: 44-207-808-2688; e-mail: james.larkin{at}rmh.nhs.uk

Received May 27, 2009; accepted for publication October 27, 2009; first published online in THE ONCOLOGIST Express on November 25, 2009.

Disclosures: Rowan E. Miller: None; James M. G. Larkin: Honoraria: Novartis, Pfizer, Bayer; Research funding/contracted research: Novartis, Pfizer, Bayer.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Outcomes for patients with advanced renal cell carcinoma (RCC) have improved significantly in recent years with the development of novel noncytotoxic systemic therapies. The multitargeted kinase inhibitors sunitinib and sorafenib have been approved for the treatment of advanced RCC, and bevacizumab, a monoclonal anti–vascular endothelial growth factor antibody, has shown significant clinical activity, both as a single agent and in combination with interferon-. The mammalian target of rapamycin inhibitors temsirolimus and everolimus have led to longer overall survival times in poor-risk patients in the first-line setting and longer progression-free survival times in kinase inhibitor refractory patients in the second-line setting, respectively.

Despite these advances, almost all patients develop resistance to treatment and cure is rarely seen. There is therefore a need to overcome resistance, induce longer lasting remissions, and improve survival. A potential approach to this is to combine active agents, and the clinical data for combination therapy with novel targeted agents in advanced RCC are reviewed here.

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