Cancer Decisions - Free Newsletter -September 2, 2007

HERE AT THE MOSS REPORTS

Back in April I published a two-part discussion of new research showing that radiation treatment given to women as a follow-up to breast cancer surgery can increase the risk of heart damage and subsequent cardiovascular disease.

To read my previous newsletters on this topic, please click or go to:

http://www.cancerdecisions.com/041507.html
http://www.cancerdecisions.com/042207.html

This research was published in the March 7th, 2007 issue of the Journal of the National Cancer Institute (Hooning 2007).

It is widely assumed that modern radiation delivery procedures have largely eliminated the danger of incidental damage to the heart. The www.breastcancer.org, Web site, for example, issues this soothing reassurance:

"Radiation therapy techniques have changed dramatically....New technology allows doctors to use the lowest dose of radiation possible. They can also more precisely target the radiation to the breast and away from the heart - so the heart receives a minimal amount or none at all."

But within the past month a study published in the Journal of Clinical Oncology has once again raised concerns about the risks of radiation-associated heart damage in women given adjuvant radiation following surgery for early breast cancer.

In this study, researchers found that the risk of cardiac abnormalities, and in particular damage to the left anterior ascending coronary artery, was very significantly raised among women who had received left sided breast irradiation for stage I and II breast cancer (Correa 2007).

CONSTANTLY MONITORING NEW RESEARCH

During my long career in the field of cancer I have witnessed many instances of new research forcing a re-examination of the complacent therapeutic assumptions of the past. By constantly monitoring the scientific literature I aim to provide my readers with the best possible synopsis of the current state of knowledge in the world of cancer treatment and prevention. My goal, and that of my organization, Cancer Communications, Inc., is to maintain the sort of consistent, reliably objective analytical standard that will allow my readers to make truly informed decisions.

In the past 30 years I have written and published extensively on the subject of cancer and its treatment, and have compiled a comprehensive series of more than 200 individual reports on different cancer diagnoses - The Moss Reports - each one of which examines both the standard treatment options that are likely to be offered for a particular cancer diagnosis, and the possible alternative and complementary approaches that may prove most useful.

If you would like to order a Moss Report for yourself or someone you love, you can do so securely and easily from our Web site, www.cancerdecisions.com, or by calling 1-800-980-1234 (814-238-3367 from outside the US).

I also offer phone consultations to clients who have purchased a Moss Report. A phone consultation can be enormously helpful in drawing up an effective treatment strategy and getting one's options clearly prioritized.

A recent phone consultation client wrote:

"I've used the Moss Report on Breast Cancer to direct my successful ten-year battle with the disease, and I've appreciated the thorough research and unbiased opinions that Dr. Moss provides. Since I am once again in a position that I must seek further treatment, I chose to have a phone consultation with Dr. Moss. I had been considering a treatment option that Dr. Moss felt very strongly would not be of benefit to me. Through our conversation I not only gained information that will keep me from wasting $20,000 on a treatment with no merit, but Dr. Moss also gave me some ideas that cause me to remain very hopeful." - J.M.

To schedule a phone consultation, please call 1-800-980-1234 (814-238-3367 from outside the US) or send an email to Jacquie@cancerdecisions.com.

We look forward to helping you.

CURRENT TOPICS

Also available from our Web site are our Current Topics reports - a series of in-depth reviews of important cancer-related subjects and controversies. Currently available are the following:

On Guard - Gardasil (An in-depth discussion of the anti-cervical cancer vaccine Gardasil)
Do Antioxidants and Chemotherapy Conflict?
Mammography, Biopsy and the Diagnosis of Breast Cancer
Herceptin or Deceptin? (An evaluation of the use of Herceptin in breast cancer)
Avastin: Your Money Or Your Life. (A clear-eyed look at the targeted drug Avastin)
The Politics of Hope: Andrew von Eschenbach and the Decline of the National Cancer Institute
The Mexican Cancer Clinics in the Era of Evidence-Based Medicine

AUDIO NEWSLETTER

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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."

To be concluded, with references, next week.

--Ralph W. Moss, Ph.D.

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IMPORTANT DISCLAIMER

The news and other items in this newsletter are intended for informational purposes only. Nothing in this newsletter is intended to be a substitute for professional medical advice.