title: Protein kinase inhibitors in renal cell carcinoma.
abstract: BACKGROUND
  Metastatic Renal Cell Carcinoma (mRCC) was historically treated with cytokine therapy with a poor outcome. In the last decade, new therapies targeting vascular endothelial growth factor (VEGF) or the mammalian target of rapamycin (m-TOR) pathways demonstrated efficacy in mRCC. Protein kinase inhibitors as well as monoclonal antibodies targeting these pathways have become the standard treatment of renal cell carcinoma (RCC) in the first-line setting and beyond.
  
  
  METHODS
  This review describes the various Phase III trials concerning protein kinase inhibitors including anti-angiogenic tyrosine kinase inhibitors (TKIs) and m-TOR serine/threonine kinase inhibitors, which have demonstrated a benefit in the treatment of mRCC. It focuses on efficacy, safety and management.
  
  
  CONCLUSIONS
  VEGF TKI and m-TOR inhibitors have significantly improved the outcome of mRCC and offer a gain in survival by sequential treatments for the majority of patients. But they induce a particular toxicity profile. An adequate management of each drug and its sequence in treatment is essential to optimise the outcome and preserve the quality of life (QoL) of patients with mRCC. In forthcoming years, pending results should indicate whether VEGF TKI are of interest in an adjuvant setting and if new drugs targeting will challenge the current standard guidelines in the metastatic setting.
authors: Hôpital Saint-André, Bordeaux University Hospital-CHU Bordeaux, Department of Medical Oncology , 1 Rue Jean Burguet, 33075 Bordeaux , France +33 5 56 79 58 96 ; alain.ravaud@chu-bordeaux.fr.
authors: Amaury
authors: A
authors: Daste
authors: Thomas
authors: T
authors: Grellety
authors: Marine
authors: M
authors: Gross-Goupil
authors: Alain
authors: A
authors: Ravaud
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020360:Neoadjuvant Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases