title: Second-line strategies for metastatic renal cell carcinoma: classics and novel approaches.
abstract: OBJECTIVE
  Renal cell carcinoma is an aggressive malignancy with a high propensity for both early and metachronous regional and distant metastasis. While surgical resection is the mainstay of therapy for patients with localized disease, the prognosis for patients with distant metastasis is poor with a 5-year survival rate of less than 10%. Response rates to first-line immunotherapy or immunochemotherapy range from 10-35%; responses achieved are predominantly partial remissions of short duration. Until today, there is no standard therapeutic procedure for the growing number of patients who relapse following first-line therapy and desire further active treatment.
  
  
  METHODS
  This article reviews classic and recent publications about second- and third-line approaches, their potential efficacy and toxicity.
  
  
  RESULTS
  Several novel approaches have raised well-founded hope. Especially the application of monoclonal antibodies targeting VEGF signalling as well as different receptor tyrosine kinase inhibitors have the potential to change the face of second-line treatment of patients with metastatic RCC. Both groups of agents are focused in current phase III trials, either as mono- and/or combination therapy.
  
  
  CONCLUSIONS
  Until today, second-line treatment of patients with metastatic RCC progressing under therapy with biological response modifiers remains an unresolved issue. The results of ongoing clinical trials evaluating novel targeted approaches can be expected with suspense.
authors.affiliation: Department of Urology, Philipps-University Medical School, Baldingerstrasse, 35043 Marburg, Germany. ajschrader@gmx.de
authors.forename: A J
authors.initials: AJ
authors.lastname: Schrader
authors.forename: Z
authors.initials: Z
authors.lastname: Varga
authors.forename: A
authors.initials: A
authors.lastname: Hegele
authors.forename: S
authors.initials: S
authors.lastname: Pfoertner
authors.forename: P
authors.initials: P
authors.lastname: Olbert
authors.forename: R
authors.initials: R
authors.lastname: Hofmann
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary*; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A