Avastin is the brand name for the anti-cancer medication bevacizumab, which belongs to a group of drugs called monoclonal antibodies. An antibody is a molecule produced by the body in response to a foreign invader or antigen. A monoclonal antibody is created in the laboratory to target and inhibit certain proteins. These agents are very specific for the molecules that they are created against and are therefore called targeted therapies.
Mechanism of action
Bevacizumab (Avastin) is a recombinant humanised monoclonal IgG1 antibody. Monoclonal antibodies recognise and lock on to specific proteins (receptors) that are present on the surface of cancer cells.
Once a monoclonal antibody attaches to the target receptor, it triggers the immune system to attack the cancer cells, which then destroy themselves. The antibody can also prevent the receptor from acting on another protein to stimulate tumor growth, proliferation or angiogenesis (blood vessel formation).
In the case of bevacizumab, the mechanism of action is inhibition of a cell surface protein called vascular endothelial growth factor (VEGF). This VEGF helps tumors to form new blood vessels and blocking VEGF stops the cancer from developing its own blood supply.
This reduces the tumor’s supply of oxygen and nutrients, therefore preventing its growth and survival. Starved of vital nutrients, the tumour stops growing and shrinks. Drugs that prevent the growth of blood vessels are termed angiogenesis inhibitors or anti-angiogenics.
The United States Food and Drugs Administration has approved bevacizumab for the first-line treatment of patients with advanced and metastatic (cancer that has spread to vital organs) carcinoma of the colon or rectum. The therapy can also be used to treat advanced non-small cell lung cancer or advanced cancer of the breast, kidney or bowel. Bevacizumab has also been used successfully in the treatment of eye disorders such as age-related macular degeneration and diabetic retinopathy, where abnormal blood vessel growth in the retina leads to leaky vessels that cause retinal damage.
Mode of administration
Bevacizumab may be given in combination with chemotherapy or when being used to treat kidney cancer, it may be given in combination with interferon. The drug is given as a drip into a vein (infusion) every two or three weeks. Bevacizumab is usually administered over a period of 90 minutes for the first infusion and 60 minutes for the second infusion, with infusions thereafter lasting for about 30 minutes.
The estimated half life (a measure of drug action duration) of bevacizumab is approximately 20 days and the time taken for the drug to reach a steady-state concentration in the blood is around 100 days. The volume of distribution is 46 mL/kg and the drug is eliminated from the body at a rate of 2.75 to 5 mL/kg/day, depending on factors such as body weight, gender and extent or size of the tumor.
There are several side effects associated with the use of bevacizumab. Side effects may occur either as a reaction to the infusion or as a response to the drug itself.
Some examples of infusion-related reactions include flu-like symptoms, skin rash, allergy, angioedema and abdominal pain. The drug itself may cause nausea, vomiting, diarrhea, constipation, loss of appetite, weakness, hypertension and mouth ulcers as well as raising the risk of bleeding disorders. Bevacizumab can also decrease the white blood cell count and make patients more susceptible to infection.