Bevacizumab for patients with metastatic renal cancer: An update

James C. Yang, Michael Gordon, Michael Atkins, Robert Motzer, Allan Lipton, Robert Flanigan, Robert Figlin, William Kaelin, Daniel George, W. Marston Linehan

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Most clear cell renal cell cancer (RCC) is caused by biallelic loss of the von Hippel-Lindau gene. One consequence of this loss is up-regulation of vascular endothelial growth factor via a pathway involving accumulation of hypoxia inducible factor. Vascular endothelial growth factor, a potent angiogenic factor, is secreted by many human cancers, but clear cell RCC as a group produces particularly high levels and has a highly vascular histologic appearance. In a randomized, placebo-controlled, double-blind trial, we tested the use of a neutralizing antibody to vascular endothelial growth factor, bevacizumab, in patients with metastatic RCC. At 3 or 10 mg/kg every 2 weeks, toxic effects were minimal, with hypertension and proteinuria the most substantial events. There were four partial responses (10% response rate) and a highly substantial prolongation of time to tumor progression in patients who received the higher dose of bevacizumab. With a crossover design and very sensitive criteria for disease progression, no difference in survival was shown. Four patients have been undergoing long-term bevacizumab therapy without tumor progression for 3 to 5 years. Three have substantial proteinuria but retain normal renal function. A small pilot trial combining bevacizumab and thalidomide showed no unexpected toxic effects. Future trials should consider combination therapies and strategies in which patients are treated through initial disease progression with antiangiogenic agents such as bevacizumab.

Original languageEnglish (US)
Pages (from-to)6367s-6370s
JournalClinical Cancer Research
Volume10
Issue number18 II
DOIs
StatePublished - Sep 15 2004

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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