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Dog's tale of survival opens door in cancer research
By Erin Kirk, USA TODAY
Navy's cancer was back. Marion Haber knew that her golden retriever pup was going to die if she didn't act fast.
"Without surgery and treatment, Navy would have had three months to live," says Haber, a fourth-year student at the Tufts University School of Veterinary Medicine in Boston. But traditional treatments, such as amputation, chemotherapy and radiation, would have meant Navy, then only 18 months old, wouldn't be able to swim at a nearby lake or go for long walks.
So Haber opted for an experimental treatment that eliminated Navy's cancer within 10 weeks without any of the side effects associated with traditional therapies.
Today, 16 months later, all traces of her cancer are gone.
Now, the same kind of treatment, named the "Navy Protocol" in honor of Haber's dog, is being tested elsewhere in veterinary medicine. And researchers are excited enough by Navy's success that they will begin testing the treatment in human cancer patients later this year. They caution, however, that it might be several years before they know whether the treatment, one of many avenues of cancer research, will work in humans. Even in veterinary medicine, Navy is their only total success.
The treatment is a cocktail of so-called anti-angiogenic drugs, which have been widely researched for more than a decade and work by starving tumors of their blood supply. Researchers say the three-drug combination, which Haber mixed into Navy's regular dog food, targets the cancer from many angles.
Haber, 24, knew about this form of experimental cancer treatment because she had worked as a research fellow at the Angiogenesis Foundation, a non-profit organization based in Cambridge, Mass. Created in 1994, the foundation promotes research on angiogenic treatments by teaming drugmakers with scientists.
Haber persuaded researchers at the foundation to design a treatment for Navy. No one thought the pup had a prayer.
Haber had first found cancer in Navy's chest while practicing examinations on the dog in September 2000. That tumor was removed by a surgeon, who to be on the safe side removed extra tissue and five ribs, replacing them with three prosthetics. When the tumor appeared on Navy's leg just weeks after the surgery, Haber knew that was very bad news. That's when she sought the anti-angiogenic treatment.
Navy's treatment began on Christmas Day 2000. By early March 2001, her veterinary oncologist could not find a trace of cancer. "That's a remarkable achievement, for the dog to have no side effects and the tumor be gone," says Judah Folkman, the father of angiogenesis.
An entirely new field
Folkman, a researcher at Children's Hospital at Harvard Medical School in Boston, discovered in the 1970s that angiogenesis â€” the growth of new blood vessels â€” plays a significant role in the development of cancer. Since his discovery, an entirely new field of cancer research has developed.
Doctors now are testing drugs that stop the growth of the blood vessels that tumors rely on for nutrients. They're known as anti-angiogenic drugs, and they deprive a tumor of its life source by killing the blood vessels that feed it.
Today, more than 50 anti-angiogenic drugs are being used as therapy for cancer patients. At least 10,000 cancer patients have been treated with anti-angiogenic drugs, and $4 billion has been devoted to angiogenic research to date. This year, the amount of money spent by the federal government and the pharmaceutical industry on cancer research is expected to exceed $10 billion.
The first clinical trial for cancer patients using anti-angiogenic drugs was conducted in 1992. In the late '90s, the popularity of anti-angiogenic drugs grew, resulting in many more clinical trials.
In 1998, when news reports suggested that anti-angiogenic drugs, such as endostatin and angiostatin, held promise that a cure for cancer was within reach, clinical trials using those drugs skyrocketed. Everyone wanted the "miracle drugs."
But researchers were chagrined that the news reports inflated the public's expectations. Folkman says those drugs should never have been painted as a cure.
Instead, he says, "the idea is to convert cancer into a chronic manageable disease."
Anti-angiogenic drugs are showing a great deal of promise in that respect. So far, researchers have been able to "freeze cancer in its tracks" in some cases using the drugs, says William Li, president of the Angiogenesis Foundation.
Doctors hope to stabilize the cancer while maintaining the patient's quality of life. The drugs have no documented side effects. They don't appear to make patients sick, and they don't cause patients to lose hair. That makes them an appealing option for humans â€” and their pets.
The field recently expanded to include veterinary medicine. Navy is viewed by some as a pioneer in veterinary oncology, and her success is raising awareness about cancer treatments for animals. And though Navy is only one dog, Folkman says the success of her treatment is important. Navy never had chemotherapy, and her cancer wasn't just stabilized â€” it vanished.
When researchers heard that Navy was cancer-free after receiving a cocktail of drugs already approved by the Food and Drug Administration â€” Celebrex, tamoxifen (sold as Nolvadex) and doxycycline â€” the treatment became known as the Navy Protocol.
Navy's treatment was designed using what researchers call a "multi-targeted" approach, meaning that each drug targets a different angiogenesis growth factor. These growth factors are like switches that "turn on" angiogenesis, signaling the body to grow new blood vessels that feed the tumors.
Using the Navy Protocol, doctors "sent in three smart bombs" to attack the growth factors, Li says. If the growth factors can't send signals to the rest of the body, angiogenesis can't take place. Then researchers can "pull the rug out from under the cancer," Li says.
What researchers have found by attacking these switches is a new method of early detection for animal cancers. Now, veterinarians can use a simple blood test to look for signs of the disease.
"If you see an elevation in an animal's angiogenic growth factors, that's a red flag to look for a tumor," says Chris Bonar, associate veterinarian at the Cleveland Metroparks Zoo. Bonar collaborated with the Angiogenesis Foundation and Antony Moore, head of the Harrington oncology program at the Tufts University School of Veterinary Medicine, to design and monitor Navy's treatment.
Navy's treatment was practical and easy. Navy snarfed the pills down every morning in her food.
Today, Navy is living a dog's life in North Grafton, Mass. Technically, her cancer is in remission, and she has periodic checkups. She spends her days chewing on a rope or playing with a fuzzy monkey that squeaks. She is always up for a walk; her tail wags at the jingle of her leash. On Haber's days off from school, she delights in taking Navy to swim at nearby ponds.
High cost of treatment
Angiogenic therapy began with humans. Now, "an unexpected benefit is being able to treat pets," Folkman says. And pets need better treatments, just as humans do.
According to a Morris Animal Foundation survey, the No. 1 concern of American pet owners today is cancer. Domestic animals are living longer because of improved health care and nutrition, so they naturally develop more cancers.
The cost of treating animal cancers is steep: Pet owners spend from $2,000 to $9,000 to save their pets' lives, according to Jack Stephens, a cancer survivor and former practicing veterinarian, who founded Veterinary Pet Insurance, based in Brea, Calif. His company offers special plans that reimburse up to $8,000 for cancer treatment.
Navy's treatment, though experimental, cost $2,000. Haber says the cost would have been about the same had she opted to give Navy chemotherapy or radiation. Donations from Haber's classmates at Tufts helped pay for the treatment.
More veterinarians are specializing in the treatment of cancer in animals. The American College of Veterinary Internal Medicine certified five veterinary oncologists this year, bringing the total to 122 specialists worldwide.
Although the Navy Protocol appears promising to cancer-ridden pets, Li says, the foundation is not pushing the cocktail as the only way to treat canine cancers. Other anti-angiogenic drugs, such as Abbott Laboratories' ABT-510 and ABT-526, also are being used in pet clinical trials.
The benefits of these drugs can be seen in zoos, too. Cancer afflicts certain species of exotic animals, such as tigers, Tasmanian devils and polar bears, as often as it does people and pets, Bonar says.
Tigers in captivity are especially prone to mammary cancers, while Tasmanian devils can develop all kinds of cancers, and polar bears tend to have a higher incidence of pancreatic cancer.
Recently, a polar bear at the Cleveland Metroparks Zoo developed an angiosarcoma, a tumor of the blood vessel, on its paw. Because the tumor was aggressive, it needed to be removed surgically, and the bear was given a cocktail of anti-angiogenic drugs as a secondary measure.
The cocktail, similar to Navy's, consisted of Celebrex, Thalidomide and doxycycline. Bonar says he "mixed the medicine up with something sweet and tasty, like cherry pie filling, and the bear gobbled it up."
Later, the bear was euthanized because of an infection unrelated to the tumor. As he did an autopsy, Bonar found the beginnings of pancreatic cancer. He believes the anti-angiogenic drugs suppressed the cancer. It would have been in its acute stages had the bear not been on the drugs, he says.
Navy gets the word out
"Cancer is an artifact of captivity because our animals generally live longer than they would in nature," he says. "It's a disease of old age."
Bonar says he has seen lymphomas and uterine cancers in primates. But, he adds, laughing, "I haven't seen lung cancers because there are no cigarette smokers among my patients."
The Cleveland Metroparks Zoo and the Angiogenesis Foundation hope that exotic animals will be among those that benefit from anti-angiogenic therapies, even if the Navy Protocol does not turn out to be the answer.
Since Navy's success, the Angiogenesis Foundation is working to help pets and their owners overcome cancer on a case-by-case basis. The foundation continues to receive telephone calls from pet owners and veterinarians who have heard about Navy.
Over the past three weeks, the foundation has helped administer the Navy Protocol to a dozen dogs. There have been changes in the dogs' tumors, but Li says it is still too early to tell whether the results will be as dramatic as Navy's.
Meanwhile, Haber says Navy is quite a celebrity in the labs of Tufts vet school.
"I'm not even Marion anymore," she says. "I'm Navy's owner."