Avastin Risks

This article appeared in my local newspaper today:

http://www.newsday.com/news/health/li-study-avastin-chemo-mix-raises-risk-1 .2654790


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Hi Cheryl!

I also read this and found it very interesting. Something to think about!


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As far as I see it with all chemo drugs there is a high risk.
I took chemo and was on Carbo/Taxol cocktail for one dose only, on the second dose I had a reaction that coudl have killed me.
I then went on Gemzar, luckily, I made it through it.
We are in desperate need of a less toxic chemo agent if there ever will be one.
It is good to be aware of these articles, so we can make more informed decisions on our care.
thank you for posting this one.

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I had weekly carbo/taxol treatments and luckily for me did not have any adverse reactions. However, I wound up having an allergic reaction almost a year later to methotrexate which I was taking for my psoriatic arthritis. Perhaps the hope for less toxic therapies will come in the form of some sort of gene therapy.

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Greg, i read the link you posted and the comments. Thanks for the helpful information. I may subject myself to another biopsy to find out about VEGF receptivity of my tumor to better weigh Avastin risk/benefit in my treatment. I just added Avastin and have had 1 treatment. I'd like more information as to how many Avastin patients have FAE and how far along in treating with Avastin the median FAE occurs. I was drawn to Avastin for it's potential to pass the blood/brain barrier, which in my case carbo/taxol apparently were not doing (though they worked great shrinking tumor everywhere else in my body. So if Avastin is too risky, what else might be safer and have a decent chance of holding brain mets in check? I just learned of a local trial with Imetelstat (telemerase inhibitor) that might be effective at combatting brain mets, but I don't know if it is more or less safe than Avastin. This poker game sure has high stakes doesn't it? Lots to talk about with my oncologist.

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If you want to learn more about the microvascular viability assay for anti-angiogenesis-related drugs.



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I was unable to read the entire article as I do not subscribe to Newsday. Is it possible to copy &paste it? If it's a very long story don't bother.
Seems that even though I subscribed to Newsday for 37 yrs, it doesn't count to allow me to read it online.

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Sorry about that. I didn't realize it would be limited. Here's the article in its entirety:

LI study: Avastin, chemo mix raises risk

When used in combination with conventional chemotherapy, the cancer drug Avastin puts patients at a greater risk of dying from side effects, a team of Stony Brook medical investigators has found.

Raising new questions about the popular medication, Dr. Shenhong Wu and colleagues studied 16 clinical trials involving more than 10,000 patients who received an Avastin/chemo combination, the method most commonly used to administer Avastin.

Their analysis of the most common causes of fatal side effects involving Avastin found that 2.5 percent of patients taking Avastin and undergoing chemo died, compared with 1.7 percent of those taking chemotherapy alone, an increased risk of 47 percentage points.

Nearly a quarter of those patient deaths of those taking Avastin and chemo were due to severe bleeding, the new analysis found. Another 12.2 percent died because their treatment destroyed infection-fighting white blood cells.

"When we consider Avastin for treatment, we have to balance the risk with the benefit," said Wu, a cancer specialist at Stony Brook University Medical Center, who has led a series of studies on Avastin in recent years.

Ed Lang, a spokesman for Avastin's maker, Genentech, said the company welcomes research about Avastin's safety, but he contends Wu's study is flawed because the results include forms of cancer for which Avastin is not approved.

In the study, appearing in Wednesday's Journal of the American Medical Association, Wu found that risks of potentially fatal side effects involve patients across a range of advanced cancers. "We initially thought this drug was less toxic," said Wu, adding that doctors have faced a steep learning curve involving Avastin, a drug approved for colorectal, lung, brain and kidney cancers.

The drug has been found to cause severe bleeding, holes in the bowel and problems with wound healing. In December, federal regulators began the process of withdrawing approval for its use as breast cancer treatment after a research review suggested it failed to help those patients live longer or provide enough benefit to outweigh its risks.

Avastin eliminates tumor blood vessels, blunting the cancer's ability to tap into the host's blood supply to withdraw nutrients. Without sustenance, a cancer, theoretically, cannot grow.

Despite the risks, Wu prescribes the drug for some patients and notes that treatment-related toxicity is also a problem with conventional cancer drugs.

Like other doctors across the country, he has found that Avastin works extraordinarily well in some patients. The problem: Doctors have no way of discerning who will fare best.

Dr. Daniel Hayes of the University of Michigan argues in an accompanying journal editorial that doctors need a way to screen patients and administer Avastin only to those who would benefit most.

"Although [Avastin] has benefit, it is currently not possible to determine in whom or for how long," Hayes said.

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Joan- Just google it--there are amny to read here's one: http://www.webmd.com/cancer/news/20110201/cancer-drug-avastin-linked-to-dea th-risk

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Thanks for the article.
Makes you think twice doesn't it? I believe this drug was also used for breast cancer. However, I believe they have stopped using it for breast cancer.

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I received 6 treatments of Taxol, Carbo and Avastin. My main problem was low platelet counts. I think on day 10 of my fourth treatment they hit a low of 30. I was struggling to keep them above 100 to start another round of chemo.

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I have done well on Avastin except for the 3rd day of 2nd treatment.Had elevated B/P in am.Fever and chills late pm same day and was in ER with,Uti,And Copd excerbation.Since thase resolved,had cantinued with Avastin,Alimta Andcarboplatin,for total of 8.Now On maintenance with having taken # $ Avastin with Alimta.My liver met disappeared for 2 Ct<s but was tiny but visible again in November at start of maintenance.Ct scheduled For/16.I have had Mediport pulled after 2 infections inAugust.Landed inn Hospital Dec 21,with Staph Epi in Groshong cath and throat with fever104.3.Week of January 16 to 18 fno fever but Hard chills.Surgeon and onc pulled GroShong Cathter on 1/19/11.Holding another Mediport till another recheck on 2/22/11.They want to be sure infection out of blood stream.Articles discuss poor healing but not in fection.Hmmmm.GP any info there,Thanks my friend.By the way I am Stage $ and feeling much better since Groshong out and finished 2 weeks of Levoquin,AndiB

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My husbands first treatment of chemo for stage 4 nsclc included Avastin. He ended up in the ICU for hemoptysis (bleeding from his lungs) and then ended up with blood clots as well. He went from a seemingly healthy (apart from the cancer issue) person to one unable to walk. After about 6 weeks I managed to get him into rehab and he slowly built up enough strength to come home. But he never was able to get back to a normal level of strength again during his remaining time with us.

I do attribute this to the Avastin. But I feel that because this was started so soon after his initial diagnosis which included a biopsy via a bronchoscopy that perhaps the lungs hadn't had time to heal properly before the avastin was started. I also think that the annoying thing about the statistics is that they probably are only the tip of the iceberg as my husbands side effects were not reported. I expressed my concern to the doctor that this get reported to the drug company but they really don't have any interest in doing this. At least if my husband is going to be a guinea pig I wanted someone to include his reaction in the general statistics.

I would caution anyone who has had any recent biopsies or surgeries or any issues with blood clots to think carefully about starting this powerful drug. Quality of life is often overlooked in the headlong jump to combat this disease but believe me it makes a huge impact on whatever time one has left.

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Small bowel obstructions can result in the compromise of venous blood in the affected segment of bowel, edema, localized tissue anoxia with ischemia, necrosis, perforation leading to peritonitis, and worse.

Avastin is associated with the risk of bowel perforations in advanced ovarian cancer. Advanced ovarian cancer commonly involves bowel walls. The problem is a direct result of the drug's ability to kill tumor cells that have replaced healthy bowel tissue, leading to a dead area that then perforates.

With conventional chemotherapy, as the tumor melts away, new connective tissue forms a patch. But Avastin can inhibit the growth of capillaries into newly forming tissue, as well as in tumor tissue. If one does not have any known bowel involvement, one would probably be okay.

Avastin has been associated with wound dehiscence. The vascular inhibitory effects predispose to these complications. Although vascular targeting is a useful adjunct to therapy, the mechanism of action may more reflect the Vascular Permeability Factor effects and less the anti-angiogenesis effects.

The same thing applies to colon cancer. If Avastin is given within at least 28 days following major surgery (or before), it results in an abscess formation. This is due to the impaired wound healing induced by Avastin.

Avastin working like it's supposed to work, not only does it cut off blood supply to the tumor, it also cuts off blood supply to the colon entirely causing the tissue to die. Avastin can cause you to loose your colon. What is distubring is oncologists' comment that this is common with Avastin, but is never mentioned until it is too late.

Most bowel perforations with Avastin have been in cases where there is tumor going right through the wall of the colon. Avastin causes the tumor to melt away, leaving a hole. With Avastin, the tumor dissolves, but scar tissue won't form because it can't make a blood supply.

Surgical oncologists may be needed for surgical aspects of management later in the course of the disease. Intestinal obstruction in the course of cancer may require operative surgical managment.

Avastin (as a single agent) is relatively ineffective in virtually all tumor types other than Renal (a disease known to be driven by the VHL->HIF1a->VEGF pathway). Beyond that it appears to better deliver the effects of other classes of drugs

Whiz bang therapies often get a pass on toxicities because they are just so darn cool (Herceptin and CHF in the adjuvant setting is another example). The problem is that few drugs work the way oncologists think and few of them take the time to think through what it is they are using them.

Source: Cell Function Analysis

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