Journal Article

A Randomized Trial of Bevacizumab, an Anti–Vascular Endothelial Growth Factor Antibody, for Metastatic Renal Cancer

Steinberg, Seth M, Topalian, Suzanne L, Hwu, Patrick, Yang, James C, Sherry, Richard M, Schwartzentruber, Douglas J, Chen, Helen X, Rosenberg, Steven A, Haworth, Leah

2003

Overview

In this randomized trial, an antibody against vascular endothelial growth factor, bevacizumab, prolonged the time to progression of disease in patients with metastatic renal-cell cancer. There was no effect on survival. Positive effects from an antibody against vascular endothelial growth factor. Studies of the hereditary form of clear-cell renal carcinoma, which occurs in the von Hippel–Lindau syndrome, led to the identification of the von Hippel–Lindau tumor suppressor gene ( VHL ). The gene is mutated both in hereditary renal-cell carcinoma (where one mutation is a germ-line mutation) and in most cases of sporadic clear-cell renal carcinoma (where both alleles have acquired mutations or deletions). 1 , 2 One consequence of these mutations is the overproduction of vascular endothelial growth factor through a mechanism involving hypoxia-inducible factor α. 3 – 7 In addition, both VHL -deficient mice and vascular endothelial growth factor–knockout mice die in utero . . .

• Publisher: Massachusetts Medical Society
• Subject: Adenocarcinoma, Clear Cell - drug therapy / Adenocarcinoma, Clear Cell - genetics / Adenocarcinoma, Clear Cell - secondary / Angiogenesis / Antibodies, Monoclonal - adverse effects / Antibodies, Monoclonal - therapeutic use / Antibodies, Monoclonal, Humanized / Bevacizumab / Cancer / Carcinoma, Renal Cell - drug therapy / Carcinoma, Renal Cell - genetics / Carcinoma, Renal Cell - secondary / Cytokines / Disease Progression / Double-Blind Method / Endothelial Growth Factors - antagonists & inhibitors / Endothelial Growth Factors - immunology / Female / Genes, Tumor Suppressor / Humans / Intercellular Signaling Peptides and Proteins - immunology / Kidney Neoplasms - drug therapy / Kidney Neoplasms - genetics / Kidney Neoplasms - pathology / Ligases - genetics / Lymphatic Metastasis / Lymphokines - antagonists & inhibitors / Lymphokines - immunology / Male / Middle Aged / Mutation / Neovascularization, Pathologic - drug therapy / Proteins / Rodents / Studies / Tumor Suppressor Proteins / Ubiquitin-Protein Ligases / Vascular endothelial growth factor / Vascular Endothelial Growth Factor A / Vascular Endothelial Growth Factors / Von Hippel-Lindau Tumor Suppressor Protein