Avastin (or bevacizumab to the scientific community) is a humanised monoclonal antibody that is directed against all biologically active forms of VEGF. Antibodies are molecules that are typically a normal part of the human immune system. An antibody is meant to bind to a very specific target which is then typically destroyed and removed by the body. Avastin is an antibody that binds VEGF and acts to block its action.
Bevacizumab was one of the first antiangiogenic agents to demonstrate activity against metastatic kidney cancer. Bevacizumab is administered intravenously every two weeks. On July 31, 2009, the FDA granted approval for the use of Avastin in combination with interferon-? for the treatment of patients with metastatic renal cell carcinoma. The approval was based on results published in the journal Lancet in 2007. In this double-blind phase III trial 649 patients with metastatic kidney cancer who had undergone nephrectomy, were randomized to either bevacizumab plus Interferon-? or placebo plus Interferon-? as a first-line treatment. Median progression-free survival of patients was significantly improved in those receiving the combination treatment including Bevacizumab and Interferon-? compared to the control group (10.2 vs 5.4 months). Response rates were also significantly improved in the Bevacizumab and Interferon-? groups (31% vs 13%). The most common severe (grade 3) toxicity was fatigue: 12% in the bevacizumab and IFN arm versus 8% in the control arm.
A second multicenter phase III trial which was performed in 2008 and which was conducted in the United States and Canada, was nearly identical in design with the exception that it lacked a placebo element and did not require prior nephrectomy. In this second study, the average progression-free survival was 8.5 months in patients receiving The combination of Bevacizumab and Interferon-? compared to 5.2 months for patients receiving Interferon-? therapy alone. The overall response rate was in favour of the combination group (25.5% vs 13.1%). However, both studies failed to show any significant difference regarding overall survival between the combination of Bevacizumab and Interferon-? versus Interferon-? alone (18.3 vs 17.4 months). |
Adverse Effects:
The addition of Bevacizumab to Interferon-? therapy was acceptable in terms of toxicity in most patients. Bevacizumab has been associated with hemorrhage (4.7-5.2%), arterial thromboembolism (4.4%), venous thromboembolism (13.6-15.1%), hypertension (8-18%), heart problems (left ventricular dysfunction) (grades 2-4: 1.7%), protein in the urine (proteinuria) (grades 3/4: 3%), gastrointestinal perforation (0-3.7%), and wound healing complications (0.8%). Gastrointestinal perforation occurred in 1% of patients in post marketing studies and generally presents as abdominal pain, constipation, emesis, and fever. Due to complications with wound healing, Bevacizumab initiation should be delayed at least 28 days after surgery. Infusion reactions can also occur with Bevacizumab (3%) and are associated with hypertension, wheezing, hypersensitivity, chest pain and rigors. |
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