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Monday, 15 March 2010

Trial Drug - Bevacizumab (Avastin)

Bevacizumab (which is also known as Avastin) is a drug that is already used in the treatment of other cancers. Oddly enough it is in the news today as one of the drugs that the NHS is allegedly "denying" cancer patients on cost grounds and also because it has failed a trial for colrectal cancer.  It was also recently in the news for failing an advanced stomach cancer trial.

It is usually involved in the treatment of advanced, often metastatic (secondary), cancers so the trial that I may be involved in represents a departure from that principle. 

It is a targeted therapy rather than a chemotherapy drug.  Cancers need to develop their own blood supply to grow and Avastin is thought to work by blocking its blood vessels.  Avastin  is thought to work by blocking a protein released by both normal cells and cancer cells.  The protein is called VEGF and is produced throughout the life of the tumour.  Avastin is a tumour starving therapy, aiming to starve the tumour of nutrients and oxygen that it needs to grow.



The tumour sends out VEGF to nearby blood vessels causing new blood vessels to grow towards the tumour (angiogenesis).



My documentation from the hospital states

"Adding bevacizumab to chemotherapy has been used to treat patients with bowel cancer, lung cancer and breast cancer and has been shown to improve the outcome of the disease.  We are now tring to find out whether this is also the case for patients with stomach cancers like yours".

This statement is perhaps a little economical with the truth as it makes no mention of the fact that current treatments are largely with advanced metastatic cancers and it also make no mention of cancers where it has not been effective. There are also a number of quite serious side effects some of which are fatal.  I'll mention those later.

Before continuing with any negative thought on the drug I want to accentuate the positive.  Remember that I have said that my primary aim is to reduce the tumour as much as possible before surgery, so as I am thinking of participating in the trial for some simple reasons
  • Avastin is believed to help deliver chemotherapy to the cancerous tissue
  • High levels of VEGF in my condition (gastric adenocarcinoma) has been shown to correlate with poor five year survival rates (so targeting VEGF would seem a reasonable strategy)
  • I can pull out of the trial at any point
  • Only 50% of those entering the trial receive Avastin - so I may not receive it even if I participate in the trial
When considering the negative aspects of the drug the following text is taken from Avastin's own website.  It should be remembered that as the data is taken from Avastin's current use it is largely from patients who have advanced cancers.  I've got strong vasculature, excellent blood pressure (on the low side if anything) and the only side effect that particularly worries me is the Gastrointestinal perforation (which can be fatal)

I am forming questions for the team based on much of this information.

Gastrointestinal (GI) perforation: Treatment with Avastin can result in the development of a potentially serious side effect called GI perforation, which is the development of a hole in the stomach, small intestine, or large intestine. In clinical trials, this event occurred in more people who received Avastin than in the comparison group (0.3% to 2.4%). In some cases, GI perforation resulted in fatality. Avastin therapy should be permanently stopped if GI perforation occurs.


Surgery and wound healing problems: Treatment with Avastin can lead to slow or incomplete wound healing (for example, when a surgical incision has trouble healing or staying closed). In some cases, this event resulted in fatality. Surgery and wound healing problems occurred more often in people who received Avastin than in the comparison group. Avastin therapy should not be started for at least 28 days after surgery and until the surgical wound is fully healed. The length of time between stopping Avastin and having voluntary surgery without the risk of having surgery and wound healing problems has not been determined. Treatment with Avastin should be stopped at least 28 days before voluntary surgery and in people with surgery and wound healing problems that require medical treatment.

Severe bleeding: Treatment with Avastin can result in serious bleeding, including coughing up blood, bleeding in the stomach, vomiting of blood, bleeding in the brain, nosebleeds, and vaginal bleeding. These events occurred up to 5 times more often in people who received Avastin. Across cancer types, 1.2% to 4.6% of people who received Avastin experienced severe to fatal bleeding. People who have recently coughed up blood (greater than or equal to a half teaspoon of red blood) or have serious bleeding should not receive Avastin. Treatment with Avastin should be permanently stopped if serious bleeding occurs (ie, requiring medical attention).

In clinical trials for different cancer types, there were additional serious, and sometimes fatal, side effects that occurred in more people who received Avastin than in those in the comparison group. The formation of an abnormal passage from parts of the body to another part (non-GI fistula formation) was seen in 0.3% or less of people. Severe to life-threatening stroke or heart problems were seen in 2.4% of people. Too much protein in the urine, which led to kidney problems, was seen in less than 1% of people. Additional serious side effects that occurred in more people who received Avastin than in those in the comparison group included severe to life-threatening high blood pressure, which was seen in 5% to 18% of people, and nervous system and vision disturbances (reversible posterior leukoencephalopathy syndrome), which was seen in less than 0.1% of people. Infusion reactions with the first dose of Avastin were uncommon and occurred in less than 3% of people, and severe reactions occurred in 0.2% of people.

Common side effects that occurred in more than 10% of people who received Avastin for different cancer types, and at least twice the rate of the comparison group, were nosebleeds, headache, high blood pressure, inflammation of the nose, too much protein in the urine, taste change, dry skin, rectal bleeding, tear production disorder, back pain, and inflammation of the skin (exfoliative dermatitis). Across all trials, treatment with Avastin was permanently stopped in 8.4% to 21% of people because of side effects.

1 comment:

  1. Just thought I would let everyone know been to the hospital today, my Husband (Mick) has got the all clear. He had the 3 rounds of chemo followed by the operation and then another 3 rounds of chemo. Looking back I wonder where the last 9 months have gone.

    Good luck with the start of the chemo, will be thinking of you and especially your poor wife who has to go through all the worrying for you.
    x

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