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Cooperative Group Bulletin Board |
or Interferon- Plus Anti-Vascular Endothelial Growth Factor Antibody (Bevacizumab) in Metastatic Renal Cell Carcinoma
1 University of California at San Francisco, San Francisco, California; 2 Cancer and Leukemia Group B Statistical Center, Durham, North Carolina; 3 University of Chicago Medical Center, Chicago; and 4 Cancer and Leukemia Group B, Central Office of the Chairman, Chicago, Illinois
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- (IFN-) 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- 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- alone or IFN- plus Avastin.
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