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Avastin
Bevacizumab
Bevacizumab (trade name Avastin, Genentech/Roche) is a humanized monoclonal antibody that recognises and blocks vascular endothelial growth factor A (VEGF-A)VEGF-A is a chemical signal that stimulates the growth of new blood vessels (angiogenesis).
Blood vessels grow uncontrollably in cancer, retinal proliferation of diabetes in the eye, and other diseases. Bevacizumab can block VEGF-A from creating new blood vessels. Bevacizumab was the first clinically available angiogenesis inhibitor in the
Bevacizumab is currently approved by the U.S. Food and Drug Administration (FDA) for cancers that are metastatic (have spread to other parts of the body). It received its first approval in 2004 for combination use with standard chemotherapy for metastatic colon cancer and non-small cell lung cancer.[2] In 2008, it was approved by the FDA for use in metastatic breast cancer, a decision that generated some controversy as it went against the recommendation of its advisory panel,[3] who objected because it only slowed tumor growth but failed to extend survival.
Clinical studies are underway in non-metastatic breast cancer, renal cell carcinoma, glioblastoma multiforme, ovarian cancer, castrate-resistant (formally called hormone refractory) prostate cancer, non-metastatic unresectable liver cancer and metastatic or unresectable locally advanced pancreatic cancer. A study released in April 2009 found that bevacizumab is not effective at preventing recurrences of non-metastatic colon cancer following surgery.[4] In May 2009, it received FDA approval for treatment of recurring Glioblastoma Multiforme, while treatment for initial growth is still in phase III clinical trial.[5]
Background
Bevacizumab is a humanized monoclonal antibody, and was the first commercially available angiogenesis inhibitor. It stops tumor growth by preventing the formation of new blood vessels by targeting and inhibiting the function of a natural protein called vascular endothelial growth factor (VEGF) that stimulates new blood vessel formation.
The drug was first developed as a genetically engineered version of a mouse antibody that contains both human and mouse components. Genentech is able to produce the antibody in production-scale quantities.
Indications
Bevacizumab was approved by the FDA in February 2004 for use in metastatic colorectal cancer when used with standard chemotherapy treatment (as first-line treatment) and with 5-fluorouracil-based therapy for second-line metastatic colorectal cancer. This recommendation was based on E3200 trial - addition of bevacizumab to oxaliplatin/5-FU/leucovorin (FOLFOX4) therapy. It was approved by the EMEA in January 2005 for use in colorectal cancer.
In 2006, the FDA approved bevacizumab for use in lung cancer in combination with standard first-line chemotherapy. A study conducted by the Eastern Cooperative Oncology Group (ECOG) demonstrated a 2-month improvement in overall survival in patients with Stage IIIb/IV non-small cell lung cancer (NSCLC). Due to the observance of severe pulmonary hemorrhage in patients with NSCLC with squamous histology in an earlier study, patients with such histology were excluded from the pivotal ECOG trial.
In 2008, the FDA approved Bevacizumab for use in breast cancer. A panel of outside advisers voted 5 to 4 against approval, but their recommendations were overruled. The panel expressed concern that data from the clinical trial did not show any increase in quality of life or prolonging of life for patients - two important benchmarks for late-stage cancer treatments. The clinical trial did show that bevacizumab reduced tumor volumes and showed an increase in progression free survival time. It was based on this data that the FDA chose to overrule the recommendation of the panel of advisers. The decision was lauded by patient advocacy groups and some oncologists. Other oncologists felt that granting approval for late-stage cancer therapies that did not prolong or increase the quality of life for patients would give license to pharmaceutical companies to ignore these important benchmarks when developing new late-stage cancer therapies.[3]
Bevacizumab is usually given intravenously through the arm every 14 days. In colon cancer, it is given in combination with the chemotherapy drug 5-FU (5-fluorouracil), leucovorin, and oxaliplatin or irinotecan.
In 2009, the FDA approved Bevacizumab for use in metastatic renal cell cancer (a form of kidney cancer) which is the drug's sixth indication[6] [7], following earlier reports of activity[8] and EU approval in 2007. Also in 2009, an FDA advisory committee unanimously recommended Bevacizumab for treatment of glioblastoma multiforme, a type of brain cancer.[9]
In the September 2009 issue of the Journal of Clinical Oncology, UCLA researchers reported that Avastin dramatically improves response and survival in patients with recurrent glioblastoma.[10]
Side effects
Bevacizumab inhibits the growth of blood vessels, which is part of the body's normal healing and maintenance. The body grows new blood vessels in wound healing, and as collateral circulation around blocked or atherosclerotic blood vessels. One concern is that bevacizumab will interfere with these normal processes, and worsen conditions like coronary artery disease or peripheral artery disease.[17]
The main side effects are hypertension and heightened risk of bleeding. Bowel perforation has been reported. In advanced lung cancer, less than half of patients qualify for treatment.[18] Posterior reversible encephalopathy syndrome,[19]nasal septum perforation, and renal thrombotic microangiopathy have been reported.[20]
These effects are largely avoided in ophthalmological use since the drug is introduced directly into the eye thus minimizing any effects on the rest of the body.
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