[Angiogenesis and renal cell carcinoma].
Developments in the knowledge of molecular biology of renal cell carcinoma (RCC) over the past 20 years have been identified. Angiogenesis is playing a key role in the physiopathology of RCC. Von Hippel-Lindau (VHL) alterations, HIFalpha accumulation and vascular endothelial growth factor (VEGF) overexpression are important mediators of this process. Several stategies have been developped to target angiogenesis for the treatment of metastatic RCC. These include inhibition of VEGF receptors (inhibition of the tyrosine kinase activity) or binding to the VEGF protein. Several additional kinases inhibitions including PDGF receptors are also targeted. Sunitinib (SU11248) is an orally biovailable small molecule that has demonstrated superiority over interferon-alpha for the treatment of metastatic RCC. In a recent randomized phase III study conducted in 750 patients, the response rate to sunitinib was 31% and to interferon 6%. The median of progression free survival (PFS) was 11 months for sunitinib and 5 months for interferon (p < 0.001). Sorafenib (BAY43-9006) was found to inhibit Raf1, but also VEGFR2 and 3, Flt3, PDGFR-a and b and c-kit, has been tested in a phase III study against placebo after one prior systemic therapy. The median of the time to progression (TTP) for sorafenib was 24 weeks versus 12 weeks for patients in the placebo arm (p = 0,01). Other molecules tested in metastatic RCC will be presented including axitinib, pazopanib and bevacizumab.
Billemont
Bertrand
B
Hôpital Pitié-Salpêtrière, Service d'oncologie médicale, 47, boulevard de l'Hôpital, 75013 Paris.
Méric
Jean-Baptiste
JB
Izzedine
Hassan
H
Taillade
Laurent
L
Sultan-Amar
Valentine
V
Rixe
Olivier
O
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000188:drug therapy; D019008:Drug Resistance, Neoplasm; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000209:etiology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011507:Proteinuria / Q000139:chemically induced; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use; D000077157:Sorafenib; D000077210:Sunitinib; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D011993:Recombinant Fusion Proteins; C475927:VEGF-Trap fusion protein, recombinant; D042442:Vascular Endothelial Growth Factors; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib