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'Bevacizumab' (trade name 'Avastin') is a monoclonal antibody against vascular endothelial growth factor. It is used in the treatment of cancer, where it inhibits tumor growth by blocking the formation of new blood vessels. Bevacizumab was the first clinically available angiogenesis inhibitor in the United States.
Bevacizumab was approved by the U.S. Food and Drug Administration in 2004 for use in combination with standard chemotherapy in the treatment of metastatic colon cancer and most forms of metastatic non-small cell lung cancer^[2]. Currently, several additional late-stage clinical studies are underway to determine its safety and effectiveness for patients with: adjuvant / non-metastatic colon cancer, metastatic breast cancer, metastatic renal cell carcinoma, metastatic glioblastoma multiforme, metastatic ovarian cancer, metastatic hormone-refractory prostate cancer, and metastatic metastatic or unresectable locally advanced pancreatic cancer.
Bevacizumab was developed by Genentech and is marketed in the United States by Genentech and elsewhere by Roche (Genentech's parent company), under the brand name 'Avastin'.

Contents

Background

Clinical use

Non oncologic uses

Side effects

References

External links

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.

Clinical use

Bevacizumab was approved by the Food and Drug Administration (FDA) in February 2004 for use in colorectal cancer when used with standard chemotherapy treatment. It was approved by the EMEA in January 2005 for use in colorectal cancer. Israel has also approved the use of bevacizumab.
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.
Bevacizumab has also demonstrated activity in renal cell cancer and ovarian cancer when used as a single agent, and in lung cancer and breast cancer when combined with chemotherapy.
January 20, 2007: Researchers reported at the 2007 Gastrointestinal Cancers Symposium that a trial of bevacizumab as an addition to chemotherapy has shown no improvement in survival of patients with advanced pancreatic cancer. It may cause higher rates of high blood pressure, bleeding in the stomach and intestine, and intestinal perforations.

Non oncologic uses

Bevacizumab has recently been used by ophthalmologists as an intravitreal agent in the treatment of proliferative (neovascular) eye diseases, particularly for choroidal neovascular membrane (CNV) in age-related macular degeneration (AMD). Although not currently approved by the FDA for such use, the injection of 1.25-2.5 mg of bevacizumab into the vitreous cavity has been performed without significant intraocular toxicity (although not studied in a contolled environment). Many retina specialists have noted impressive results in the setting of CNV, proliferative diabetic retinopathy, neovascular glaucoma, diabetic macular edema, and macular edema secondary to retinal vein occlusions.
Ranibizumab, a Fab fragment derived from the same parent molecule as bevacizumab, has been developed by Genentech (by the same scientist Napoleone Ferrara) for intraocular use. This drug, under the trade name 'Lucentis', now has FDA approval. It has undergone extensive clinical trials. Reports indicate substantially better outcomes in patients treated with inravitreal Lucentis than conventional treatments in people with choroidal neovascularization (wet age related macular degeneration). Most patients with choroidal neovascularization lose vision or at best maintain vision despite treatment with laser, photodynamic therapy or Macugen. A much larger proportion (up to 70%) gained vision with Lucentis. Lucentis is however very expensive ($1500-2000 per injection, - the studies were done with monthly intravitreal injections). Bevacizumab is significantly cheaper (<$100 a shot versus >$1500) it appears to be safe (at least in the short term) and many doctors have noticed improvements in vision and outcomes similar to those seen with Lucentis. As Genentech has developed both drugs it has little interest in seeing Bevacizumab use in the eye and it is likely to remain off label. Off-label use of this medication has created significant controversy in medical retina and vitreo-retinal surgery.
The National Eye Institute (NEI)--of the National Institutes of Health (NIH)--announced in October 2006 that it would fund a comparative study trial of ranibizumab (Lucentis®) and bevacizumab (Avastin®) to assess the relative safety and effectiveness in treating AMD.
The Lions Eye Institute (LEI) announced in July 2006 it was running a clinical trial with bevacizumab on 100 patients, and that the results were positive.
http://www.abc.net.au/news/newsitems/200607/s1677557.htm

Side effects

Several adverse side effects have been reported with bevacizumab. The main side effects of concern are hypertension and heightened risk of bleeding. Studies done particularly in lung cancer have shown that less than half of the patients with advanced disease qualify for treatment with this drug.^[1]
Bowel perforation has also rarely been reported.
The FDA updated the label on the drug on September 25 2006, to note rare cases of brain capillary leak syndrome and nasal septum perforation.

References

1. The Proportion of Patients with Metastatic Non-small Cell Lung Cancer Potentially Eligible for Treatment with Bevacizumab: A Single Institutional Survey, Vamsidhar Velcheti, Avinash Viswanathan, Ramaswamy Govindan, , , Journal of Thoracic Oncology, 2006 Full text

2. Avastin Prescribing Information, Genentech Inc., October 2006, www.clinicaltrials.gov

External links

★ Avastin.com

★ Avastin-info.com Information for healthcare professionals outside of the US

★ Avastin Information from Chemocare.com

★ A Cancer Drug Shows Promise, at a Price That Many Can't Pay ''New York Times'', February 15, 2006, Alex Berenson

★ NCI Drug Information Summary on Bevacizumab for Patients

★ NCI Drug Dictionary Definition for Bevacizumab

★ Phase II Clinical Trial of Bevacizumab for Adenocarcinoma of the Pancreas