Avastin® (bevacizumab) Proposed Mechanism of Action
Genentech continues to study the mechanism of action of Avastin and role of VEGF and anti-VEGF therapy at various stages of tumor development. The mechanism of action of Avastin has been elucidated in preclinical studies.
1. Tumors release the VEGF protein causing nearby blood vessels to sprout new vessels — a process called angiogenesis. These blood vessels feed the growth of the tumor. They also provide a "highway" for tumor cells to spread to other parts of the body.1
2. Avastin is a therapeutic antibody that specifically binds to the VEGF protein — a potent source of angiogenesis.1
3. Avastin may block the tumor's ability to communicate with nearby blood vessels and may prevent the tumor from connecting to the blood supply.1
4. Studies have shown that targeting the VEGF protein with Avastin may interfere with a tumor's ability to grow.1
Avastin, in combination with intravenous 5-fluorouracil based chemotherapy, is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum. Avastin is not indicated for adjuvant treatment of colon cancer.
Avastin, in combination with carboplatin and paclitaxel, is indicated for first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer.
Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.
BOXED WARNINGS and Additional Important Safety Information
Possible Serious Side Effects
Everyone reacts differently to Avastin therapy. So it's important to know what the side effects are. Although some people may have a life-threatening side effect, most do not. Your doctor will stop treatment if any serious side effects occur. Be sure to contact your health care team if there are any signs of these side effects.
Most serious side effects (not common, but sometimes fatal):
- GI perforation— A hole that develops in your stomach or intestine. Symptoms include pain in your abdomen, nausea, vomiting, constipation, or fever
- Wounds that don't heal— A cut made during surgery can be slow to heal or may not fully heal. Avastin should not be used for at least 28 days before or after surgery and until surgical wounds are fully healed
- Serious bleeding— This includes vomiting or coughing up blood; bleeding in the stomach, brain, or spinal cord; nosebleeds; and vaginal bleeding. If you recently coughed up blood or had serious bleeding, be sure to tell your doctor
Other possible serious side effects
- Abnormal passage in the body— This type of passage—known as a fistula—is an irregular connection from one part of the body to another and can sometimes be fatal
- Severe high blood pressure— Blood pressure that severely spikes or shows signs of affecting the brain. Blood pressure should be monitored every 2 to 3 weeks while on Avastin and after stopping treatment
- Kidney problems— These may be caused by too much protein in the urine and can sometimes be fatal
- Infusion reactions— These were uncommon with the first dose (less than 3% of patients). 0.2% of patients had severe reactions. Infusion reactions include high blood pressure or severe high blood pressure that may lead to stroke, trouble breathing, decreased oxygen in red blood cells, a serious allergic reaction, chest pain, headache, tremors, and excessive sweating. Your doctor or nurse will monitor you for signs of infusion reactions
- Severe stroke or heart problems— These may include blood clots, mini-stroke, heart attack, and chest pain. These can sometimes be fatal
- Nervous system and vision problems— Signs include headache, seizure, high blood pressure, sluggishness, confusion, and blindness
Side effects seen most often
In clinical studies across different types of cancer, some patients experienced the following side effects:
- High blood pressure
- Too much protein in the urine
- Rectal bleeding
- Back pain
- Taste change
- Dry skin
- Inflammation of the skin
- Inflammation of the nose
- Watery eyes
Avastin is not for everyone.
Talk to your doctor if you are:
- Undergoing surgery— Avastin should not be used for 28 days before or after surgery and until surgical wounds are fully healed
- Pregnant— Data have shown that Avastin may harm your unborn baby. Use birth control while on Avastin. If you stop Avastin, you should keep using birth control for 6 months before trying to become pregnant
- Planning to become pregnant— Taking Avastin could cause a woman’s ovaries to stop working and may impair her ability to have children
- Breastfeeding— Breastfeeding while on Avastin may harm your baby and is therefore not recommended
If you have any questions about your condition or treatment, talk to your doctor.
You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.
Please see full Product Information, including Serious Side Effects, for additional important safety information.