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Therapeutic Advances in Medical Oncology
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Review: Systemic therapy for advanced renal cell carcinoma

James M.G. Larkin

Department of Medicine, Royal Marsden Hospital, London SW3 6JJ, UK, james.larkin{at}rmh.nhs.uk

Emma L.S. Kipps

Department of Medicine, Royal Marsden Hospital, London SW3 6JJ, UK

Ceri J. Powell

Department of Clinical Oncology, Royal Marsden Hospital, London SW3 6JJ, UK

Charles Swanton

CR-UK Translational Cancer Therapeutics Laboratory, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK

Renal cell carcinoma (RCC) accounts for approximately 3% of all cancers and is refractory to cytotoxic chemotherapy - immunotherapy has until recently been the standard of care for advanced disease. Randomised trials reported in the last 5 years have demonstrated that a number of agents including the monoclonal antibody, bevacizumab, and the kinase inhibitors - sorafenib sunitinib, temsirolimus and everolimus - are active in advanced RCC. Bevacizumab is directed against the vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, whilst sorafenib and sunitinib inhibit a number of targets including the VEGF and platelet-derived growth factor (PDGFR) receptor tyrosine kinases. Temsirolimus and everolimus inhibit the intracellular mammalian target of rapamycin (mTOR) kinase. Sunitinib and temsirolimus have demonstrated efficacy in comparison with immunotherapy in the first-line setting in patients with favourable and poor prognosis advanced disease respectively. In the second-line setting, everolimus has shown benefit over placebo in patients who progress following treatment with a VEGF receptor tyrosine kinase inhibitor and sorafenib has demonstrated efficacy in comparison with placebo in patients with immunotherapy-refractory disease. We review here recent clinical trial data and discuss future developments in the systemic treatment of RCC including combination and sequential therapy, adjuvant therapy, the role of biomarkers and the prospects for the development of rational mechanism-directed therapy in this disease.

Key Words: renal cell carcinoma • bevacizumab • sorafenib • sunitinib • temsirolimus • everolimus

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Therapeutic Advances in Medical Oncology, Vol. 1, No. 1, 15-27 (2009)
DOI: 10.1177/1758834009338430
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