Novel treatments for metastatic renal cell carcinoma.
The mainstay of any curative treatment in renal cell carcinoma (RCC) is surgery. In case of metastatic disease at presentation a radical nephrectomy is recommended to good performance status patients prior to start of interferon-alfa treatment. Interferon-alpha (IFN-alpha) offers in a small but significant percentage of patients advantage in overall survival; interleukin-2 (IL-2) based therapy gives similar survival rates. To date hormonal and chemotherapy do not have a proven impact on survival. The recent new insights in the molecular biology of clear RCC has revealed a key-role for vascular endothelial growth factor (VEGF) in the stimulation of angiogenesis in this highly vascularized tumour. This opens interesting new treatment strategies including: blockage of VEGF with the monoclonal antibody bevacizumab and inhibition of VEGF receptor tyrosine kinases (with small oral molecules such as SU11248 or PTK787). Likewise, inhibition of the Raf kinase pathway (with oral Bay 43-9006) or inhibition of the mTOR pathway (with i.v. CCI-779) are under investigation. Preliminary clinical results with all these compounds are interesting and the results of ongoing phase III studies will become available in the next years.
Department of Medical Oncology 550, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. d.vanspronsen@onco.umcn.nl
D J
DJ
van Spronsen
P F A
PF
Mulders
P H M
PH
De Mulder
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends; D007680:Kidney Neoplasms / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy*; D009362:Neoplasm Metastasis / Q000503:physiopathology / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D048490:raf Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D066246:ErbB Receptors; D058570:TOR Serine-Threonine Kinases; D048490:raf Kinases