Encouraging one year results in vessel growth factor trial

November 11, 2000

NEW ORLEANS, Nov. 12 - In one of the largest follow-up studies to date, researchers have shown that gene therapy for heart disease may relieve chest pain and does not increase the risk for cancer, according to a study reported today at the American Heart Association's Scientific Sessions 2000. Since gene therapy is used to stimulate the growth of new blood vessels, there has been concern that therapy may lead to overgrowth of other cells in the body, increasing the risk for cancer or other problems.

Among 102 patients in the study, there were no significant differences in deaths, heart attacks or cancer over the course of one year, whether they received placebo or a high or low dose of the protein used in the gene therapy.

"The long-term safety looks excellent," says lead author Timothy D. Henry, M.D., director of interventional cardiology at Hennepin County Medical Center and associate professor of medicine at the University of Minnesota in Minneapolis. "There was no increase in adverse events, which some scientists have suggested might occur. If anything, it looks as if there is a lower rate of adverse events in patients getting the higher dose."

A new concept in heart research is that prodding new vessel growth will increase the blood flow to the heart in people whose arteries are narrowed by fatty deposits. Such deposits reduce the flow of blood and oxygen to the heart, which can cause chest pain known as angina. The deposits can also trigger heart attacks.

The protein, called vascular endothelial growth factor (VEGF), is produced by the body and initiates the growth of new blood vessels, a process called angiogenesis. VEGF is one of a number of proteins involved in vessel growth.

Researchers are exploring two ways to use it: One is gene therapy, in which the gene that commands cells to produce VEGF is introduced into heart cells, that will then produce the protein. The other approach, which Henry and his colleagues used, is to treat patients with the VEGF protein. The study included individuals who participated in the VEGF in Ischemia for Vascular Angiogenesis (VIVA) trial. The 178 patients in that study all suffered severe angina, almost 90 percent had undergone at least one bypass operation, and almost 75 percent had undergone at least one angioplasty to open their narrowed arteries.

Participants received a placebo, 17 nanograms of VEGF, or 50 nanograms of VEGF per kilogram of body weight each minute during four treatments. In the first treatment, participants received their dose by infusion directly into the heart arteries for 20 minutes. On the third, sixth, and ninth days after their initial therapy, they received a 4-hour intravenous infusion.

The study participants were followed for four months. Results of the initial VIVA trial were reported at the American Heart Association's Scientific Sessions in 1999. Those in the follow-up study reported today were tracked for another eight months.

"One of the prominent findings of the VIVA trial was a very strong placebo effect; even the placebo patients got better," Henry says. "In the follow-up study we wanted a longer-term look at the safety of VEGF itself and at this placebo effect as well."

Theoretically, stimulating new blood vessel growth could increase a person's risk of cancer or a heart attack. A cancer tumor requires blood vessels to grow to a life-threatening size. If a person had a tumor the size of a pinhead, there was a question of whether giving VEGF might spur vessel growth into the cancer and cause it to grow. "That didn't happen," Henry says.

One study in animals also suggests that if tiny new blood vessels grow into the walls of arteries, these new vessels might speed up the growth of fatty deposits or make them more likely to rupture and cause a heart attack. That scenario also failed to play out.

"The incidence of death and heart attack in this group of high risk patients was surprisingly low," Henry says.

At the end of one year, 3 percent of the placebo group, 6 percent of the low-dose, and none of the high-dose VEGF group had died. Three percent of those receiving the placebo, none of the low-dose, and 6 percent of the high-dose group had suffered a heart attack.

As for cancer, 8 percent on placebo, 3 percent on low-dose VEGF, and no one on the high dose developed cancer. Overall, 26 percent of the placebo group, 22 percent of the low-dose group, and 13 percent of those on high-dose VEGF died, had a heart attack, developed cancer, or required a revascularization procedure, such as bypass surgery.

The effect on patients' angina was also encouraging, Henry says. He reports that after one year, those in the high-dose group had less chest pain than the placebo group.

"The findings are encouraging, but certainly not conclusive," he says. "On the other hand, it's the best data we have so far in this field, and it is strong evidence that VEGF protein is safe. This is an initial study that needs to be confirmed with additional studies."
Co-authors are George R. McKendall, M.D.; Michael A. Azrin, M.D.; John Lopez, M.D.; Raymond Benza, M.D. James T. Willerson, M.D.; John Giacomini, M.D.; Rachel Olson, R.N.; Bradley A. Bart, M.D.; Joseph P. Roel, B.S.; and Brian H. Annex, M.D.

NR00-1193 (SS2000/Henry)

American Heart Association

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.