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Avastin (Bevacizumab)

  • Wednesday, 07 October 2009 22:40
  • Last Updated Friday, 25 November 2011 02:25
  1. What is Avastin?
  2. Is Avastin approved for the treatment of glioblastoma multiforme in the UK?
  3. How does Avastin work?
  4. What are Monoclonal Antibodies?
  5. What is VEGF?
  6. What is Angiogenesis?
  7. How is Avastin given?
  8. Possible side effects
  9. When to contact your doctor or health care provider
  10. Monitoring and testing
  11. Additional Information
  12. Published Research


What is avastin?

Avastin is a Cancer medicine that interferes with the growth of cancer cells by blocking the formation and growth of new blood vessels in the Tumor which slows their growth.

Avastin is used to treat a certain type of brain tumor as well as cancers of the kidney, colon, rectum, lung, or breast. Avastin may also be used for purposes other than those listed here.

Avastin was recently approved by the FDA in the USA for the treatment of glioblastoma with progressive disease following prior therapy as a single agent.


Is Avastin aproved for the treatment of Glioblastoma Multiforme in the UK?

At the present time Avastin is not approved by NICE for the treatment of Glioblastoma Multiforme in the UK.

You may find the following document useful When a drug for cancer is not available on the NHS


How does Avastin work?


1. Tumours 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 tumour's ability to communicate with nearby blood vessels and may prevent the tumour from connecting to the blood supply.1
4. Studies have shown that targeting the VEGF protein with Avastin may interfere with a tumour's ability to grow.1

What are Monoclonal Antibodies?

Monoclonal antibodies are a relatively new type of "targeted" cancer therapy. Antibodies are part of the Immune System. Normally, the body creates antibodies in response to an antigen (such as a protein in a germ) entering the body. The antibodies attach to the antigen in order to mark it for destruction by the body's immune system. In the laboratory, scientists analyze specific antigens on the surface of cancer cells (target) to determine a protein to match the antigen. Then, using animal and human proteins, scientists work to create a special antibody that will attach to the target antigen. Antibodies will attach to matching antigens like a key fits a lock. This technology allows treatment to target specific cells, causing less toxicity to healthy cells. Monoclonal antibody therapy can be done only for cancers in which antigens (and the respective antibodies) have been identified.

Avastin works by interfering with the process of angiogenesis by targeting and inhibiting human vascular endothelial growth factor (VEGF).


What is VEGF?

Vascular endothelial growth factor (VEGF) is a chemical signal produced by cells that stimulates the growth of new blood vessels. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate.

VEGF's normal function is to create new blood vessels during embryonic development, new blood vessels after injury, and new vessels (collateral circulation) to bypass blocked vessels.

When VEGF is overexpressed, it can contribute to disease. Solid cancers cannot grow beyond a limited size without an adequate blood supply; cancers that can express VEGF are able to grow and metastasize. Drugs such as Avastin (bevacizumab) can inhibit VEGF and control or slow those diseases.


What is Angiogenesis?

Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over this, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for new blood vessel formation by splitting off existing ones.

Angiogenesis is a normal and vital process in growth and development, as well as in wound healing. However, it is also a fundamental step in the transition of tumors from a dormant state to a Malignant one.

In the context of cancer, tumor angiogenesis is the creation of a network of blood vessels that supplies tumors with essential nutrients and oxygen, and removes waste products.2

In 1989, Napoleone Ferrara, M.D., and a team of scientists at Genentech first isolated human vascular endothelial growth factor (VEGF), a protein now believed to be one of the most potent sources of angiogenesis.2, 3 The need for oxygen and nutrients triggers tumor cells to produce and release the VEGF protein, which leads to the formation of new blood vessels to feed the tumor. In addition to supporting tumor growth, these new vessels provide a "highway" along which tumor cells can travel through the bloodstream to other parts of the body. This may lead to the formation of new tumors and spread of cancer (metastasis). Sustained angiogenesis is a hallmark of most, if not all cancers.4 Without angiogenesis, a tumor would not likely grow beyond a few millimeters, the size of an average pencil eraser.3


How is Avastin given?

Avastin is given through an infusion into a vein (intravenous, IV). The first dose is given over 90 minutes. The infusion time can eventually be shortened to 30 minutes if well-tolerated.

The amount of avastin that you will receive depends on many factors, including your height and weight, your general health or other health problems, and the type of cancer or condition being treated. Your doctor will determine your dose and schedule.8


Possible side effects 8

Important things to remember about the side effects of avastin:

  • Most people do not experience all of the side effects listed.
  • Side effects are often predictable in terms of their onset and duration.
  • Side effects are almost always reversible and will go away after treatment is complete.
  • There are many options to help minimize or prevent side effects.
  • There is no relationship between the presence or severity of side effects and the effectiveness of the medication.
  • There is no data as to the frequency of adverse reactions that may be attributed to avastin alone. (In clinical studies avastin was used in combination with other Chemotherapy medications).

The following side effects are common (occurring in greater than 30%) for patients taking avastin:

  • Generalized Weakness
  • Pain
  • Abdominal pain
  • Nausea & vomiting
  • Poor appetite
  • Constipation
  • Upper respiratory infection
  • Low white blood cell count. (This can put you at increased risk for infection.)
  • Proteinuria (see kidney problems)
  • Nose bleed (see bleeding problems)
  • Diarrhea
  • Hair loss
  • Mouth sores
  • Headache

These side effects are less common side effects (occurring in about 10-29%) of patients receiving avastin:

  • Shortness of breath
  • Dizziness
  • High blood pressure
  • Weight loss
  • Muscle aches and pains

Not all side effects are listed above. Some that are rare (occurring in less than 10% of patients) are not listed here. However, you should always inform your health care provider if you experience any unusual symptoms.8


When to contact your doctor or health care provider:

8 Contact your health care provider immediately, day or night, if you should experience any of the following symptoms:

  • Fever of 100.5º F (38º C) or higher, chills (possible signs of infection)
  • Severe bleeding
  • Shortness of breath, difficulty breathing

Monitoring and testing

You will be checked regularly by your health care professional while you are taking avastin, to monitor side effects and check your response to therapy. Periodic blood work to monitor your complete blood count (CBC) as well as the function of other organs (such as your kidneys and liver) will also be ordered by your doctor.8

Additional Information 7


    • Can I drink alcohol while taking Avastin? - Yes, but in moderation.

    • Can I work while taking Avastin? - You may continue to work, providing you feel fit enough to do so.

    • Can I drive while taking Avastin? - Yes, there is no evidence that Avastin affects driving ability.

    • Can I exercise while taking Avastin - Its a misconception that exercise should be avoided following a diagnosis of cancer or during treatment. Light exercise can help fight fatigue, reduce the risk of blood clots and improve mood.

    • Will I have to change what I eat or drink? - No, you can eat and drink as normal.

  • The chemotherapy that you are taking may cause hair loss but Avastin will not make this worse.

  • Avastin does not affect your sex drive and you should be able to continue sexual relations. If you are a fertile male or female contraceptive precautions should be taken.

  • 8For both men and women: Do not conceive a child (get pregnant) while taking avastin . Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.

  • Don’t breastfeed while taking Avastin or for 6 months after treatment is stopped.

  • If you need to visit your GP for any other reason tell him or her you are taking Avastin

  • You should not stop taking other prescribed medication without discussing it with your doctor. Likewise discuss first before taking purchased over the counter drugs, including herbal remedies.


Published Research

To find a comprehensive list of research papers on Avastin click here.

* September 22nd 2009 - Press release from Roche 'Avastin could play an important role in improving the daily lives of patients with the most aggressive form of brain cancer' download the PDF version here


References:

1 Ranieri G, Patruno R, Ruggieri E, Montemurro S, et al. Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: from the biology to the clinic. Curr Med Chem. 2006; 13: 1845-1857

2Rosen LS. Clinical experience with angiogenesis signaling inhibitors: focus on vascular endothelial growth factor (VEGF) blockers. Cancer Control. 2002;9:36-44.

3 Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted antiogenic mitogen. Science. 1989;246:1306-1309.

4 Ranieri G, Patruno R, Ruggieri E, Montemurro S, Valerio P, Ribatti D, Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: from the biology to the clinic. Curr Med Chem. 2006;13:1845-1857

5 Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57-70.

6. Genentech

7. Cancernet

8. Chemocare


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