Bevacizumab also called Avastin is a drug used to treat some forms of cancer. It is a synthetic version of a human monoclonal antibody from the IgG1 subclass against the protein called vascular epithelial growth factor. This medicine is used alone or along with chemotherapeutic regimens in the treatment of patients with metastatic lung, breast, colon and rectal cancer. By targeting and destroying vascular epithelial growth factor it inhibits the growth of new blood vessels making it an angiogenesis inhibitor. This inhibition of angiogenesis prevents the growth of some tumors.
It was the first angiogenesis inhibitor medication to be introduced into the United States. The US FDA approved its use when combined with other chemotherapeutic agents in 2004. In June 2006, the FDA approved Avastin in combination with intravenous chemotherapy for the treatment of metastatic colorectal cancer in patients who have been previously treated for their cancer or are on second-line metastatic colorectal cancer treatments. In October 2006, the FDA approved Avastin in combination with carboplatin and paclitaxel for the first-line treatment of patients with advanced, recurrent or metastatic non-squamous non-small cell lung cancer that are unable to be removed by surgery.
The drug was discovered by scientists at Genentech and is sold in the US by Genentech and around in the world by Roche under the trade name Avastin. In the initial stages of the development of bevacizumab, it was made as a laboratory engineered mimic of an existing mouse antibody, containing both mouse and human structures. Now it is only the human version of the antibody. It is obviously unrealistic for a pharmaceutical company to try to harvest commercial volumes of antibodies from either humans or animals; hence they produce a synthetic version developed in a laboratory.
Bevacizumab works by blocking the function of vascular endothelial growth factor (VEGF), a potent pro-angiogenic factor responsible for increasing blood vessel development during cancer growth and progression. Bevacizumab therapy results in a decrease in the blood supply to the tumor and helps to slow or stop tumor growth.
Clinical trials using bevacizumab showed that it was effective in reducing tumor olumes. Bevacizumab has also been shown to increase the length of time that patients remain tumor free during and after treatment. Bevacizumab is also involved in controlling the regression of existing micro-vessels to help arrest tumor growth and reduce tumor size. Another function of the drug is that it makes the existing blood vessels in tumors that survive the drug therapy normalized, making theses blood vessels more conducive to effective anti-cancer therapy. Data accumulated from research show that VEGF may play a broad role in a range of cancers and Avastib targets VEGF, making it a promising therapy. Currently a global development program is underway for Avastin. It includes more than 300 clinical trials in 20 different tumor types, including early-stage cancers.
Bevacizumab is most often given by an IV in the arm once every 2 weeks. For colon cancer treatment, it is prescribed along with other chemotherapy drugs such as irinotecan, leucovrin, 5-FU and oxaliplatin. Bevacizumab also has been successfully used alone in the treatment of renal cell cancers and ovarian cancers. In contrast, it is used in combination chemotherapy for the treatment of breast and lung cancer. It has been reported in medical journal articles that it is ineffective in the treatment of gastrointestinal cancers when used in combination with chemotherapy. Unfortunately, it does not increase the survival time of those with advanced pancreatic cancer.
Clinically, bevacizumab has been used for many other applications although many are not FDA approved. More recently, eye doctors have been using bevacizumab in the vitreous of the eye to treat some eye diseases. One such use is with choroidal neovascular membrane, a condition in age-related macular degeneration where unusually placed blood vessels causes a loss of vision. Opthalmologists use bevacizumab in the vitreous of the eye to treat this condition without any major complications. Other diseases states that have been improved with impressive results by treatment with bevacizumab include: proliferative retinopathy and macular edema associated with diabetes; neovascular glaucoma; and other instances of retinopathy.
The mechanism of action of bevacizumab, that is its ability to inhibit the growth of blood vessels or angiogenesis, makes it a very attractive and desirable agent in the treatment of human cancers. However, angiogenesis is required as part of the body’s normal healing and maintenance. Our body needs to make new blood vessels in many physiological and pathological states. Take for example in wound healing and in collateral circulation around blocked or atherosclerotic blood vessels. One primary concern with the routine use of bevacizumab is that it will interfere with these normal processes, and worsen conditions like coronary artery disease or peripheral artery disease. It has been shown to increase the incidence of high blood pressure, bleeding in the stomach and intestine, and intestinal perforations.
The major side effects reported with bevacizumab administration include high blood pressure or hypertension and a heightened risk of bleeding. Some reports indicate that bowel perforation can also occur. Brain capillary leak syndrome, nasal septum perforation, and renal thrombotic microangiopathy have also been reported. Other side effects associated with bevacizumab use includes, dry mouth, cough, voice changes, pain, loss of appetite, diarrhea, constipation, mouth sores, nausea, and headaches.
