Recent advances in the treatment of renal cell carcinoma and the role of targeted therapies

• Published in: European journal of cancer (1990) Vol. 44; no. 15; pp. 2152 - 2161
• Main Authors: Chowdhury, Simon, Larkin, James M.G, Gore, Martin E
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-10-2008; Elsevier
• Subjects: Angiogenesis Inhibitors - therapeutic use; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antineoplastic Agents - therapeutic use; Benzenesulfonates - therapeutic use; Bevacizumab; Biological and medical sciences; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - secondary; Everolimus; Hematology, Oncology and Palliative Medicine; Humans; Indoles - therapeutic use; Kidney Neoplasms - drug therapy; Kinase inhibitor; Medical sciences; Metastatic renal carcinoma; Niacinamide - analogs & derivatives; Pharmacology. Drug treatments; Phenylurea Compounds; Protein Kinase Inhibitors - therapeutic use; Pyridines - therapeutic use; Pyrroles - therapeutic use; Sirolimus - analogs & derivatives; Sirolimus - therapeutic use; Sorafenib; Sunitinib; Temsirolimus; Tumors; Sunitinib; Metastatic renal carcinoma; Sorafenib; Temsirolimus; Kinase inhibitor; Everolimus; Bevacizumab; Antineoplastic agent; Carcinoma; Targeted therapy; Monoclonal antibody; Metastasis; Cancerology; Grawitz tumor; Advanced stage; Protein synthesis inhibitor; Antiangiogenic agent; Protein-tyrosine kinase; Kidney disease; Urinary system disease; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Lactone; Malignant tumor; Macrolide; Vascular endothelium growth factor; Treatment; Kinase; Kidney cancer; Multikinase inhibitor; Cancer
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2008.06.028

Abstract Immunotherapy confers a small but significant overall survival advantage in metastatic renal cell carcinoma (RCC) but only for the minority of patients, i.e. the 20% with good prognostic features. Recent developments in the molecular biology of renal cell carcinoma have identified multiple pathways associated with the development of this cancer. Several strategies have been investigated targeting these pathways, with significant clinical benefits shown in early studies. New agents including the small molecule targeted inhibitors sunitinib, sorafenib and temsirolimus, and the monoclonal antibody bevacizumab have shown anti-tumour activity in randomised clinical trials and have become the standard of care for most patients. Sunitinib and temsirolimus have shown significant improvements in progression-free survival (sunitinib) and overall survival (temsirolimus) in separate phase III studies in the first-line setting when compared with interferon-α. Sorafenib has demonstrated prolonged progression-free survival in a phase III study in comparison with placebo in the second-line setting. More recently two phase III studies have compared bevacizumab and interferon-α with interferon-α alone. Both studies showed a statistically significant improvement in progression-free survival for the combination arm. Additional studies are needed to optimise the use of these agents by identifying those patients who most benefit and elucidating the best way of delivering them, either in combination or as sequential single agents.