http://www.washingtonpost.com/...
AND:
http://abcnews.go.com/GMA/OnCall/story?id=3580510
( Video also at this same link )
Microchips Linked to Cancer in Animals
Study Raises Questions About Risks to Humans Who Have Had the Chips Implanted
Implanted microchips would help keep track of people with Alzheimer's disease
in case they get lost, but new concerns about the chips' safety have been
raised.
From GMA
Sept. 10, 2007
Microchips implanted in humans, a highly touted health care innovation, may
actually be a health hazard, according to a new report.
The microchips, first implanted in pets, are encoded with information about
the animal and are meant to get them home safely if lost.
Those chips are now being implanted in some people, especially Alzheimer's
patients, and encoded with their medical records. The Food and Drug
Administration called the microchip one of 2005's top innovative technologies.
The microchips have been implanted in hundreds of people like Ida Frankel,
who has Alzheimer's disease. If she gets lost and ends up in a hospital, doctors
can scan her arm and get all of her medical records.
But when the government approved these chips for use in humans three years
ago, it didn't mention that there were studies showing that similar chips caused
malignant tumors in lab rats and mice.
Cancer doctors who spoke to The Associated Press, which broke this story, say
you can't make the leap between cancer in mice and cancer in humans.
But Dr. Robert Benezra, the head of the Cancer Biology Genetics Program at
Sloan-Kettering Hospital, said, "There's no way in the world, having read this
information, that I would have one of those chips implanted in my skin."
The head of Verichip Corp., the company marketing the microchips to humans,
said it had no idea about those studies.
"We recognize that we have a corporate responsibility to review these
studies, to look at other studies, to do new studies if necessary, and do what is
appropriate after reviewing all the information in all regards, and we intend to
do this," said Scott Silverman, the chairman and CEO of Verichip.
Perhaps the more immediate concern is for household pets -- thousands of whom
have had microchips implanted. One veterinarian, though, said the risk of a
pet getting lost is much greater than the risk of cancer.
"The risk of getting lost and ending up at the pound and maybe getting put to
sleep is a bigger risk in the big picture," said Dr. Nicholas Dodman, of the
Tufts Cumming School of Veterinary Medicine.
While the microchip's potential risks may be worth it for pets, doctors
recommend further studies about the risks for humans.
NEW DOUBTS ON SAFETY OF 'TARGETED' DRUGS - PART I
New doubts have been raised about the safety and efficacy of drugs known as angiogenesis inhibitors. These drugs are designed to block the development of new blood vessels within and around tumors. Without an effective and independent blood supply a tumor cannot grow bigger than the tip of a pencil.
This strategy for combating cancer was first put forward in the early 1970s by Judah Folkman, MD, of Harvard Medical School (Folkman 1971). Folkman believed that drugs based on his research would not only be more effective but far safer than traditional cytotoxic chemotherapy. After an initial period of intense resistance, well described in Robert Cooke's 2001 book,Dr. Folkman's War, the idea caught on big time. There are now thousands of articles on angiogenesis and cancer, hundreds of them by Folkman himself. More importantly, many of the newly approved cancer drugs are based on this concept of attacking the tumor's blood supply. But while the theory itself is elegant, and Folkman has become an icon of modern medicine, there are serious questions about how safe and effective many of the current generation of anti-angiogenic drugs are in controlling tumor growth.
A study from the University of California at Los Angeles (UCLA), published in August, 2007 in the peer-reviewed journal Cell, shows that a widely used group of anti-angiogenesis drugs is associated with serious and potentially deadly side effects. These drugs are known as VEGF inhibitors. (VEGF stands for vascular endothelial growth factor, a signaling protein that promotes the growth of new blood vessels.)
Outside In vs Inside Out
Many of the currently used VEGF inhibitors such as Avastin (bevacuzimab) work by blocking VEGF signaling from outside the cell. But the UCLA researchers are trying to understand what happens when VEGF signaling is blocked from within the cell, which is a mechanism used by some of the newer, small molecule anti-angiogenic drugs that are currently in late phase clinical trials. According to a UCLA press release, "the result was unexpected, and sobering." More than half of the mice in the study suffered heart attacks and fatal strokes. The mice that remained alive developed serious systemic vascular disease, according to Luisa Iruela-Arispe, a professor of molecular, cell and developmental biology and director of the Cancer Cell Biology program at UCLA's Jonsson Cancer Center (Lee 2007).
"This was an extremely surprising result," said Iruela-Arispe, who is past president of the North American Vascular Biology Organization and a national expert on angiogenesis. "I think this study is cause for some caution in the use of angiogenesis inhibitors in patients for very long periods of time and in particular for use of those inhibitors that block VEGF signaling from inside the cell."
It is already known that 5 percent of patients taking Avastin develop blood clot-related side effects. But because Avastin was approved only three years ago, it is unclear what adverse effects may occur when patients remain on the drug for many years, according to Iruela-Arispe.
In her three-year study, Iruela-Arispe created mice that were missing VEGF in the endothelial cells that line the inside of blood vessels and form the interface between circulating blood and the vessel wall. The UCLA team did not expect to see much of an effect because the amount of VEGF that is created inside endothelial cells is tiny compared to the amount created outside the same cells. But they soon had a bombshell finding: 55 percent of the mice died by 25 weeks of age, which is the equivalent of age 30 in humans. The remaining mice lived on, but were all very ill for the remainder of their lives.
"Some side effects have already been identified in people taking angiogenesis inhibitors," said Iruela-Arispe. "And they've been along the lines of what we're seeing in the lab."
Oddly, even high levels of VEGF outside the cells did not compensate for the absence of very tiny amounts within the cells. The missing internal VEGF had "a tremendous biological significance," Iruela-Arispe said. "Clearly there is signaling from inside the cell that is different from signaling initiated outside the cell," she added. "When there is no VEGF signaling inside the cell, the endothelial cells die. The intracellular part of the VEGF signaling loop is required for cell survival. This is the first demonstration that intracellular signaling is an important event."
NEW DOUBTS ON SAFETY OF 'TARGETED' DRUGS - PART II
(This week we conclude, with references, the article we began last week on the dangers associated with the class of drugs known as angiogenesis inhibitors.)
One of the most pressing concerns surrounding current angiogenesis inhibitors is the fact that they are associated with an increased risk of thrombosis ( blood clots). Why does this happen? UCLA Prof. Luisa Iruela-Arispe's study in the August 24, 2007 issue of Cell throws light on this urgent question.
"I believe the survival function of VEGF signaling is mediated from both outside and inside the cell. When we block it from the inside, the outside signaling cannot compensate. But when we block it from the outside, maybe the inside signaling can compensate. That would explain the lesser side effects found when using drugs such as Avastin, which block the extracellular signaling."
This aspect of angiogenesis inhibitors troubles Iruela-Arispe. Avastin, like most angiogenesis inhibitors, is generally infused systemically (i.e., given via a vein directly into the bloodstream). But Iruela-Arispe, who continues to believe in the therapeutic potential of angiogenesis inhibitors, thinks they could be made safer and more effective if they were delivered in a more tumor-focused way. "There is enough smoke in the sky here to make me feel there may be a fire," she added, ominously.
Personally, I share her concerns. Over the past six years, in this newsletter, I have frequently expressed skepticism about many of the best-publicized 'targeted' drugs. My reluctance to jump on the targeted therapy bandwagon has been based on my reading of the medical literature. Simply put, the current approach, at least with the present generation of anti-angiogenic drugs, is not particularly effective. As to toxicity, while these drugs were initially promoted as non-toxic magic bullets, there is now accumulating evidence of toxicity and sometimes lethal side effects.
The interested reader can find dozens of my articles on targeted therapies by searching for terms such as Avastin, Erbitux and Iressa at my Web site, www.cancerdecisions.com.
Avastin
Since Dr. Iruela-Arispe cited the example of Avastin, let us look briefly at its track record of safety and effectiveness. In February 2004, the US Food and Drug Administration (FDA) approved Avastin (whose scientific name is bevacizumab) for advanced colorectal cancer. On October 11, 2006, FDA further approved the drug for use in combination with carboplatin and paclitaxel, for advanced or recurrent non-small cell lung cancer (NSCLC).
Approval for lung cancer was based on what FDA officials called a "significant improvement in overall survival (OS)" (Cohen 2007). An Eastern Cooperative Oncology Group (ECOG) study showed that in patients who had received no prior chemotherapy, the overall survival was 10.3 months in those receiving conventional chemotherapy vs. 12.3 months in those also receiving Avastin. One little-publicized fact was that women given Avastin showed no survival benefit at all - which will doubtless come as a shock to the families of the many women who have been given the drug nonetheless. Also notice that the test group had received no prior chemotherapy, which makes them more likely to achieve a favorable outcome: those whose disease is progressing despite having previously received chemotherapy start off in a less favorable category.
Meanwhile, about one-quarter of those receiving the combined therapy faced severe or life-threatening adverse events. Patients receiving Avastin had a four times greater chance of pulmonary hemorrhage, for example. They also faced a significantly heightened risk of gastrointestinal perforation and hemorrhage, central nervous system infarction, gastrointestinal perforation, and myocardial infarction.
The most common adverse events in patients receiving Avastin are weakness, pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, mouth sores (stomatitis), constipation, upper respiratory infection, difficulty breathing (dyspnea), extreme rashes (exfoliative dermatitis), and protein in the urine (proteinurea), according to the FDA (Cohen 2006).
All this for the possibility of two months' increased survival. And this is not to mention the stress engendered by the expense of the drug: Avastin costs approximately $8,800 per month.
The phrase 'targeted therapy' certainly has a nice ring to it. But the fact that these drugs can cause so many devastating adverse effects yet still be called 'targeted' represents a triumph of public relations over science.
http://www.cancerdecisions.com/090907.html
