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At MU veterinary hospital, dogs help test human cancer treatments

Wednesday, June 5, 2013 | 6:00 a.m. CDT; updated 1:54 p.m. CDT, Monday, June 10, 2013
Randy Wildebrandt listens to Jeffrey Bryan as he examines Jazzy on April 8 at the MU Veterinary Medical Teaching Hospital. Jazzy has an inoperable cancer tumor in her leg and is part of a comparative oncology test in an effort to learn about human cancer treatments.

COLUMBIA — The master and his dog are both very nervous.

On a Thursday morning in April, Randy Wildebrandt has brought Jazzy, a black, 14-year-old poodle, to the MU veterinary hospital for an examination of a cancerous tumor on her right hind leg. She will be injected with a radioactive liquid for a PET, or positron emission topography scan to determine whether her treatment is shrinking the tumor, then she'll spend a day in isolation while the radiation wears off.

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Wildebrandt insists that Jazzy knows something unpleasant will happen, and he could be right. His other poodles, Shasta and Cory, are playing. Jazzy stands trembling, turning her head this way and that to look at the other dogs in the lobby.

"She knows this isn't how it's supposed to be," Wildebrandt says. "This isn't normal Jazzy. This is her stressed out."

They are joined by Karen Howe, a graduate student in the College of Veterinary Medicine, who collects a sample of Jazzy's urine and a journal used to track her health. She patiently answers a barrage of questions from Wildebrandt:

Yes, Shasta can keep Jazzy company in isolation.

Yes, there's plenty of space to run around.

Yes, there are toys for her to play with.

No, they can't bring a bed that Jazzy is used to sleeping in.

Wildebrandt tells Howe, in detail, about the last times Jazzy ate, drank, peed and pooped.

Howe promises to call him that evening to let him know how his dog is doing.

"And that'll be to say, 'She's doing fine, you can pick her up tomorrow,'" she assures him.

After issuing one last anxious instruction — that Jazzy likes to be walked "happy, confident" — Wildebrandt hands Howe the two dog leashes.

"It's fine," Wildebrandt says, holding Cory's leash while Howe walks down the hospital corridor with Shasta and Jazzy. "I'm really happy for her to make this contribution. I am."

That "contribution" could help save a life someday. Maybe even Wildebrandt's wife.

Help from man's best friend

Jazzy is one of several dogs receiving experimental treatments through the comparative oncology program at MU. Veterinarians hope they can examine the dogs' responses to the treatments to learn new ways of fighting cancer in humans.

Dogs are good test subjects because of all the things they have in common with humans, said Christina Mazcko, a program manager at the Comparative Oncology Trials Consortium, a network of 20 universities that run cancer trials on pets.

Dogs tend to get the same types of cancer as humans; some of the same genetic glitches that cause cancer in humans occur in dogs. The variety of canine breeds means dogs have a lot of genetic diversity, as do humans. Their body size is closer to ours than most other pets.

Running trials on dogs is relatively fast because their bodies react quickly. So canine trials are typically much shorter than those in humans, lasting only one or two years, Mazcko said. And veterinary care is cheaper than medical care for humans, lowering the costs of the trials.

The abundance of pet dogs in our society makes them a convenient source for trial participants. There were more than 78 million pet dogs in the United States in 2012, according to the Humane Society.

Dogs have been used in trials for human cancer treatments since at least the 1960s, when bone marrow transplants were tested on them. MU began running comparative oncology trials in the early '80s, when it tested Quadramet, a drug that fights bone tumors, on pet dogs. The trials were successful, sending the drug on its path to the open market.

Since the university joined the consortium in 2007, more than 100 dogs have been entered in trials evaluating treatments for bladder cancer, prostate cancer, breast cancer, melanoma and other diseases.

An enduring enemy

Deborah and Randy Wildebrandt have been feeling that spot on Jazzy's right hind leg every week for years. Cancerous tumors there had been surgically removed twice before. When they felt a new tumor in January, it seemed harder than the others had been.

Jeffrey Bryan, their veterinarian at MU, gave the Wildebrandts these options: have the leg amputated; schedule another surgery; or, given her age, keep Jazzy comfortable while nature takes its course.

Or, he said, they could enter her in an experimental trial that, if successful, could eliminate the tumor with less pain than surgery and keep Jazzy mobile so she could continue her favorite hobby: going on walks. They chose the latter.

"We want to keep Jazzy going as long as we can," Randy Wildebrandt said.

Jazzy's well-being wasn't the only factor in their decision. In 2007, Deborah Wildebrandt endured her own bout of cancer that left the couple devoted to improving treatment of the disease.

While reflecting on her cancer, Deborah Wildebrandt kept returning to one memory. It was an afternoon in 2007, and the couple were sitting at their kitchen counter in O'Fallon, wracked with worry. Through a speakerphone, an employee from Genomic Health Inc. was explaining the results of an Oncotype DX test that would predict the chance of Deborah's breast cancer returning.

The news was unsettling and confusing: The test showed a 25 percent chance of a recurrence. Yet after a mastectomy, she had been told she had only a 4 percent chance of recurrence.

"I was scared," Deborah Wildebrandt said. "I was upset, but I was really, really scared."

She had already endured a lot of "mental angst" in coping with the mastectomy. "I'm not losing a hand, not losing a leg; it's not that essential a body part," she finally reasoned.

Now she realized her struggle was far from over. She began five years of an estrogen suppression program and five months of chemotherapy to lower the risk of recurrence.

"The experience is spooky," Deborah Wildebrandt said of the chemo treatments. "The nurses are gloved up and masked to not touch this stuff, and it's dripping into your veins. This is poison. Years later, they'll look back on this and think, 'This is barbaric.'"

The cancer hasn't returned, but Deborah has felt chronic pain all over her body — back, legs, shoulders, neck — over the past year. Doctors haven't found the source of the pain, but the Wildebrandts suspect it's a result of the chemo.

So when it came time to make a decision about Jazzy's recurring cancer, Deborah's experience informed the couple's reasoning.

Worried as they are about their pet, they're proud that she's involved in an effort that seeks better treatments and cures for cancer, so others might be spared their trauma.

"New approaches like this can stop the disease or cure it," Randy Wildebrandt said. "We're excited that Jazzy's doing this, that she's part of a field of study to help other dogs and people."

Quest for the 'holy grail' of treatment

In the MU trial, Jazzy's tumor is injected with Clostridium Novyi NT, a bacterium found in soil that causes infectious black leg disease in cattle. Clostridium grows only in places with low oxygen, such as tumors, which helps keep it from spreading to the rest of her body.

The hope is that when Jazzy's immune system mobilizes against the clostridium, it will recognize the malignant tumor and attack it as well.

"Getting the body to recognize a tumor as an invader and something that shouldn't be there is the holy grail of being able to cure cancer," Bryan said.

Clostridium is already being tested on humans in clinical trials, but the canine trial could help doctors learn how to better calibrate treatments. They want to know what amounts of the bacterium are most effective, and why the immune systems of some patients respond while others don't. By looking at the characteristics of dogs that benefit from the treatment, they hope to figure out which humans should be treated with it. They might be able to modify patients' immune systems to make them similar to those of the dogs who responded well.

The clostridium trial began when a pharmaceutical company approached MU and offered to sponsor a study using the bacterium. MU has promised not to release the company's name.

Some trials are subsidized by universities, cancer charities and animal foundations, but most are proposed and funded by pharmaceutical companies hoping to bring a new drug to the market. Bryan estimates that MU has worked with a half-dozen companies on trials since joining the consortium in 2007. The cost to fund a study can range from the tens of thousands dollars to more than a million.

As part of the trial, Jazzy's treatment has been free except for an initial examination fee the Wildebrandts paid. The cost to trial participants varies, but treatment through a trial program almost always costs less than getting treatment through a private veterinarian.

The path from clinical trials with animals to approving a drug for human use is long and arduous. Before beginning a trial, veterinarians consult MU's Animal Care and Use Committee, which oversees animal research; the committee examines the ethics of the trial and helps design a plan.

The veterinarians involved try to make sure that pet owners, who must sign a consent form, understand the experimental nature of the trials and the risks involved.

"Whenever we treat cancer, there's a risk of death from treatment," Bryan said. "I try to explain that very carefully to people."

Once the trial is complete, the veterinarians send their records to the U.S. Food and Drug Administration, which decides whether the treatment can advance to clinical trials with human subjects. The treatment then faces three rounds of human trials before it can enter the open market.

It took 16 years for Quadramet, which fights bone tumors, to make its way from MU canine trials to human treatment. MU veterinarians Jimmy Lattimer and Louis Corwin Jr. spent four years testing the drug on dozens of pet dogs before the first phase of human testing began at the Ellis Fischel Cancer Center in 1987. The drug became available to patients in 1999.

Returning home

It's a rainy Thursday afternoon in early May, almost four months after Jazzy's tumor appeared. Randy Wildebrandt is sitting in the lobby of the veterinary hospital, holding a McDonald's coffee in one hand and Shasta and Cory's leashes in the other. A small pouch containing doggie treats and plastic bags is attached to his belt; he always wears it when he takes his dogs out.

Wildebrandt is waiting for Jazzy to emerge from the clinic, where she spent the day while her veterinarians performed a biopsy on her tumor.

He's in good spirits. The results of the PET scan haven't come back yet, but Jazzy's tumor has become softer and smaller. In January, it was round and hard, but now it feels like a squishy quarter. The veterinarians tell him its size has been reduced 28 percent.

Jazzy has responded better to the clostridium than most of the other dogs in the trial. Bryan plans to look at the data he's collected from her to see whether there's something about her immune system or her tumor that has made the treatment so successful.

With the tumor in check, the Wildebrandts have two choices for further treatment. Bryan could try to cut out the tumor, but so little tissue remains on Jazzy's leg after her previous surgeries that it could be risky. They prefer the second option: Keep a close eye on the tumor, and give Jazzy another clostridium injection if it grows again.

A veterinarian brings Jazzy into the lobby and walks her to Wildebrandt. Shasta and Cory's tails wag wildly, and the three of them greet each other, noses to tails.

After a short conversation about Jazzy's next appointment, where they'll discuss the biopsy results, Wildebrandt leads the dogs outside to the wet parking lot and lifts them into his van.

He has a routine for driving with the dogs: He covers them with their favorite blankets to keep them calm. Leaning into the van, he carefully covers Jazzy with her green blanket, which she's had since 1998. Then he walks around his car in the drizzle and gets behind the wheel.

Jazzy seems excited to be going home, where Deborah Wildebrandt, whose pain has kept her from accompanying the dog to the clinic, awaits her. And as always, wherever Deborah goes, Jazzy is sure to follow.

Supervising editors are Jacqui Banaszynski and Katherine Reed.


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