title: Cancer and Leukemia Group B 90206: A randomized phase III trial of interferon-alpha or interferon-alpha plus anti-vascular endothelial growth factor antibody (bevacizumab) in metastatic renal cell carcinoma.
abstract: The majority of sporadic clear cell renal cell carcinoma (RCC) is characterized by loss of heterozygosity of the von Hippel-Lindau (VHL) tumor suppressor gene and somatic inactivation of the remaining VHL allele. The resulting VHL gene silencing leads to induction of hypoxia-regulated genes including vascular endothelial growth factor (VEGF). Thus, therapeutic inhibition of VEGF holds promise for treatment of this historically refractory malignancy. An antibody to VEGF (bevacizumab, Avastin) has demonstrated a significant prolongation of time to disease progression compared with placebo in patients with metastatic RCC. Interferon-alpha (IFN-alpha) is a standard initial cytokine therapy in RCC with a modest response rate and a survival advantage demonstrated in randomized trials. We hypothesized that the addition of anti-VEGF therapy to IFN-alpha would prolong survival in untreated metastatic RCC patients. A Phase III trial is now being conducted randomizing untreated, metastatic clear cell RCC patients to IFN-alpha alone or IFN-alpha plus Avastin.
authors.affiliation: University of California at San Francisco, San Francisco, California 94115, USA. brini@medicine.ucsf.edu
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: John
authors.initials: J
authors.lastname: Taylor
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Richard L
authors.initials: RL
authors.lastname: Schilsky
mesh_terms: D000483:Alleles; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D000860:Hypoxia; D016898:Interferon-alpha / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology; D051794:Von Hippel-Lindau Tumor Suppressor Protein
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016898:Interferon-alpha; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human