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Reprinted
from USA TODAY online
A new 'leash'
on life
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 — the growth
of new blood vessels — plays a significant role in the development
of cancer. Since his discovery, an entirely new field of cancer research
has developed. Treating cancers in pets
Common cancers
in pets
Lymphoma, or cancer of the lymph system, affects both cats
and dogs of all breeds.
Breast cancer affects both cats and dogs of all breeds.
Osteosarcoma, or cancer of the bones, is specific to large breeds of
dogs because it attacks long bones.
Oral melanoma is very common in dogs and less common in cats.
Tumors in mast cells — connective tissue beneath the skin —
are common in cats and dogs. This is the only cancer that does not have
a human correlate.
Leukemia, a cancer of bone marrow, occurs in cats and dogs but is less
common than other cancers.
Cancer symptoms
in pets
New or enlarging lumps
Unexplained weight loss
Persistent vomiting or diarrhea
Overall weakness
Abdominal swelling
Lethargy
Nasal or oral bleeding
Severe unexplained lameness
Malodorous mouth
Unexplained cough
Helpful links
Animal Cancer Foundation: www.acfoundation.org
Veterinary Pet Insurance: www.petinsurance.com
Veterinary Cancer Society: www.vetcancersociety.org
Morris Animal Foundation: www.morrisanimalfoundation.org
Perseus Foundation: www.perseusfoundation.org
Angiogenesis Foundation: www.angio.org
Source: Animal Cancer Foundation; USA TODAY research
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."
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Please
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Smedley
is on Celebrex, tamoxifen, and doxycycline.
Unlike
the polar bear, whose medicine was cherry pie flavored, Smedley's
"cocktail" is meat-flavored. |
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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 — 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 — it vanished.
When researchers
heard that Navy was cancer-free after receiving a cocktail of drugs already
approved by the Food and Drug Administration — Celebrex, tamoxifen
(sold as Nolvadex) and doxycycline — 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." |
