Targeted therapies in metastatic renal cell carcinoma: the light at the end of the tunnel.
The year 2006 will mark a turning point in the daily management of patients with metastatic renal cell carcinoma. The impact of immunotherapy with interferon-alpha or interleukin-2 has been shown to be restricted to a minority of patients. The growing understanding of molecular mechanisms involved in the pathogenesis of the disease, especially clear-cell carcinoma, has led to the development of multiple targeted therapies with significant clinical benefits. Two compounds that predominantly inhibit the tyrosine kinase activity of the vascular endothelial growth factor receptor have been shown to improve the progression-free survival of patients in first- (sunitinib versus interferon-alpha) or second-line (sorafenib versus placebo) treatment. Temsirolimus, an agent that inhibits the serine-threonine kinase activity of the mammalian target of rapamycin, offers better overall survival than interferon in patients with poor-risk characteristics. Further studies are needed to determine the optimal combinations of these agents in metastatic disease and to assess their impact in the adjuvant setting.
Pouessel
Damien
D
Department of Medical Oncology, CRLC Val d'Aurelle, Parc Euromédecine, 34298--Montpellier Cedex 5, France.
Culine
Stéphane
S
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000627:therapeutic use; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000556:secondary* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D005544:Forecasting; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007167:Immunotherapy; D007211:Indoles / Q000627:therapeutic use; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000628:therapy*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011494:Protein Kinases / Q000187:drug effects; D011725:Pyridines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077157:Sorafenib; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007155:Immunologic Factors; D007211:Indoles; D016898:Interferon-alpha; D007376:Interleukin-2; D009363:Neoplasm Proteins; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; D000068258:Bevacizumab; C401859:temsirolimus; D000077157:Sorafenib; D011494:Protein Kinases; C546842:MTOR protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases; D000077210:Sunitinib; D020123:Sirolimus