It is used in combination with standard chemotherapy drugs in patients with metastatic colorectal cancer. The U.S. Food and Drug Administration approved bevacizumab for use in colon cancer 2004. The medicine 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.
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.
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.
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. 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.
A modified fragment of the bevacizumab antibody (the FAB fragment) has been developed by Genentech (by the same scientist Napoleone Ferrara) for intraocular use. This drug ranibizumab (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, photdynamic therapy or Macugen. A much larger proportion (up to 54%) gained vision with Lucentis. Lucentis is however very expensive ($1500-2000 per injection, - the studies were done with monthly intravireal 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. The off-label used of this medication has created significant controversy in medical retina and vitreo-retinal surgery.
Faqs about Evastin
What is Avastin used for? Avastin is used with intravenous 5-FU based chemotherapy (IFL) as the first-treatment or second-treatment for patients with metastatic colon cancer (cancer of the colon or rectum that has spread to other areas of the body). IFL is a commonly used chemotherapy (medicine used to kill cancer cells) combination containing irinotecan, 5-fluorouracil (5-FU), and leucovorin for the treatment of colon cancer. Avastin will not cure colorectal cancer that has spread. Overall, patients given Avastin plus intravenous 5-FU based chemotherapy had more tumors that shrank and survived about five months longer than patients given only intravenous 5-FU based chemotherapy. In addition, the average time before tumors restarted growing or new tumors appeared was four months longer than patients who were given only intravenous 5-FU based chemotherapy.
Special Warning(s) with Avastin:
- Avastin may cause gastrointestinal perforation (holes in the stomach, intestines or colon) requiring surgery to repair.
- Avastin may impair wound healing or cause wounds to open up. Avastin should not be started for at least 28 days following major surgery and full wound healing, and should be stopped before a scheduled surgery.
- Some patients with non–small cell lung cancer (for which Avastin is not approved) treated with chemotherapy and Avastin had bleeding from the lung tumor, spitting up of blood, leading to death.
- Avastin may cause a severe increase in blood pressure so patients receiving Avastin should have their blood pressure checked regularly.
- Avastin may cause proteinuria (protein in the urine, a sign of kidney damage).
- Avastin may cause congestive heart failure (failure of the heart to pump blood well).
General Precautions with Avastin:
- Avastin should be used with caution in patients who are allergic to Avastin or to any of the ingredients in Avastin.
- Avastin may cause severe infusion reactions such as trouble breathing during the first or later doses.
What should I tell my healthcare provider?
Tell your healthcare provider if you:
- have or had liver or kidney problems
- have high blood pressure
- have congestive heart failure or other heart problems
- are pregnant, are trying to become pregnant, or are breast-feeding
- if you have recently had surgery or are planning to have surgery
Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Some medicines may affect how Avastin works or Avastin may affect how your other medicines work.
What are some possible side effects of Avastin? (This list is NOT a complete list of side effects reported with Avastin. Your healthcare provider can discuss with you a more complete list of side effects.)
Serious side effects include of Avastin treatment include:
- gastrointestinal perforation
- impaired wound healing
- severe bleeding
- a dangerously high increase in blood pressure
- kidney damage
- congestive heart failure
More common side effects of Avastin treatment include:
- tiredness and weakness
- stomach pain
- high blood pressure
- nausea and vomiting
- loss of appetite
- mouth sores
- lung infections
- nose bleeds
- shortness of breath
- decreased white blood cells
- skin peeling
- protein in the urine
- 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
- Drugs firm blocks cheap blindness cure The Guardian, June 17, 2006, Sarah Boseley