Pet dog with tumor pioneered treatment Pet dog with tumor ...

HHeeaalltthhPet dog with tumor pioneered treatment - San Francisco Chronicle http://www.sfchronicle.com/health/article/Pet-dog-with-tumor-pion...

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treatmentPet dog with tumor pioneered treatment - San Francisco Chronicle http://www.sfchronicle.com/health/article/Pet-dog-with-tumor-pion...

Courtesy Of Anita Ziebe

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HealthPet dog with tumor pioneered treatment - San Francisco Chronicle http://www.sfchronicle.com/health/article/Pet-dog-with-tumor-pion...

Gracie's tumor was treated with a trial process that may help humans.

Pet dogSuzanneLeigh with tumor pioneered
June 5, 2013

treatment
When Gracie, an 11-year-old Jack Russell terrier, was diagnosed with a malignant brain

tumor after a seizure, owner Anita Ziebe of Napa was presented with three options.

They could do nothing, which would mean that her "bouncy little dog that followed me
everywhere" would probably die within three months; she could have surgery, which might
prolong her life for up to six months; or she could undergo a clinical trial using a novel
delivery system of a cancer drug - prognosis unknown.

Ziebe, a registered nurse, picked the last,
not knowing that Gracie would become a
trailblazer in an upcoming trial at UCSF in
which human patients will undergo the
same experimental treatment.

"Brain tumors in dogs are very similar to
brain tumors in people. Some features are
virtually indistinguishable, both under the
microscope and in neuroimaging," said Dr.
Peter Dickinson, a veterinary neurologist
who led the canine trial at the School of Veterinary Medicine at UC Davis, which is
partnering with UCSF.

The type of tumors that develop in older dogs, as well as their rate of occurrence, parallel
brain tumors in humans, making pet dogs more appealing to scientists than lab rodents, the
mainstay of preclinical studies.

"Learning about brain tumors in people from mice has limitations, because these tumors

develop artificially, following the injection of human brain tumor cells," Dickinson said.

These lead to "very uniform tumors that do not reflect the complexity and heterogeneity of

human brain tumors." Courtesy Of Anita Ziebe

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Gracie's tumor was treated with a trial process that may help humans.

HealthPet dog with tumor pioneered treatment - San Francisco Chronicle http://www.sfchronicle.com/health/article/Pet-dog-with-tumor-pion...
Suzanne Leigh

GrJaucneie5,w20a1s3the first of 18 pet dogs studied in the trial of a unique drug delivery technique

designed by two UCSF neuro experts to prolong the lives of people with fatal brain tumors.
When Gracie, an 11-year-old Jack Russell terrier, was diagnosed with a malignant brain

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treatmentdramatically so, or remained stable for prolonged periods. It is difficult to quantify success,

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prolong her life for up to six months; or she could undergo a clinical trial using a novel

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prZomieibsien,ga. registered nurse, picked the last,

not knowing that Gracie would become a

trailblazer in an upcoming trial at UCSF in

which human patients will undergo the

same experimental treatment.

"Brain tumors in dogs are very similar to
brain tumors in people. Some features are
virtually indistinguishable, both under the
microscope and in neuroimaging," said Dr.
Peter Dickinson, a veterinary neurologist
who led the canine trial at the School of Veterinary Medicine at UC Davis, which is
partnering with UCSF.

The type of tumors that develop in older dogs, as well as their rate of occurrence, parallel
brain tumors in humans, making pet dogs more appealing to scientists than lab rodents, the
mainstay of preclinical studies.

"Learning about brain tumors in people from mice has limitations, because these tumors
develop artificially, following the injection of human brain tumor cells," Dickinson said.
These lead to "very uniform tumors that do not reflect the complexity and heterogeneity of
human brain tumors."

1 o3f 8of 8 5 of 8 6/5/13 10:51 AM 6/56/1/53/1130:1501:5A1

Gracie was the first of 18 pet dogs studied in the trial of a unique drug delivery technique

designed by two UCSF neuro experts to prolong the lives of people with fatal brain tumors.
HealthPet dog with tumor pioneered treatment - San Francisco Chronicle
http://www.sfchronicle.com/health/article/Pet-dog-with-tumor-pion...

More than half the dogs responded to treatment with tumors that receded, sometimes
Courtesy Of Anita Ziebe

dUrCamDaavtiisc'aDllry. Pseote,roDrircekminsaoinnewdithstGabralceief,otrhepfirorsltoonfg1e8dpeptedroiogsdws.hIotseistudmifofirscurelctetioveqduaannetwify success,

btreecatamuesnet tthhaet emnady pprooilnont gispueospulae'lslyliveeus.thanasia, a decision made by the owners who use very

Pet dog with tumor pioneereddifferent criteria in determining when the time is appropriate, Dickinson said.

Following a scan, Gracie had a biopsy to confirm her diagnosis of grade III astrocytoma, and

treatmentstarted treatment in February 2006. Every six weeks she traveled to Davis to have MRIs and

But some dogs lived longer than a year - which might equal seven years in canine time - and
drug infusions delivered directly to the tumor, via burr holes in the skull.
three dogs died of old age, results that Dickinson and his colleagues at UCSF believed were

p"Grormaciiseinlogv.ed to play with squeaky toys. That never changed throughout the trial. She had a

good appetite, didn't lose weight or seem sick. She showed no side effects or symptoms of the

tumor," said Ziebe, whose love for her canine companion prompted her to start a hospital pet

therapy program and become a certified dog trainer.

Gracie's tolerance of the treatment was fairly typical of the dogs, with no permanent side
effects noted - a finding that has caused a quiet commotion among brain tumor specialists at
UCSF.

Drugs to treat brain tumors in humans are typically taken orally or intravenously, but a major
challenge is that they do not cross the blood-brain barrier in sufficient quantities to attack the
tumor. Increasing dosage is not feasible because of systemic side effects, such as nausea,
vomiting and neutropenia, a condition in which a type of white blood cell plummets, making
the patient vulnerable to life-threatening infections.

Bypassing a barrier

Bypassing this systemic route is one solution. About a decade ago Drs. Krystof Bankiewicz
and John Park of UCSF's department of neurological surgery embarked on a project using a
drug that would be toxic to the tumor and a delivery system that would be exquisitely targeted
to reach the tumor alone.

The upshot was CPT-11, an existing cancer drug called ironotecan that Park modified by
encapsulating it into oil droplets that would remain inactive until they reached their
destination. Bankiewicz developed a complex device in which a thin tube is inserted through
a port attached to the skull. The drug is injected through the tube, which is removed after
infusion. To maximize safety and efficacy, neurosurgeons track the drug's distribution
throughout the tumor in real time, via MRI.

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HealthPet dog with tumor pioneered treatment - San Francisco Chronicle http://www.sfchronicle.com/health/article/Pet-dog-with-tumor-pion...

Cause for hope

Pet dog with tumor pioneeredA study on lab mice with brain tumors, published earlier this year in the journal Neuro-

Oncology, shows there might be cause for optimism. Researchers led by Bankiewicz and

treatmentcolleague David James compared CPT-11 treated in the usual manner with its administration

directly to the tumor. Those in the latter group were found to have fewer tumors and
improved survival. "Apparent cure," as evidenced by imaging, was noted in some mice.

Brain tumor specialists at UCSF are now waiting for FDA approval to start recruiting human
patients with the most challenging tumors: recurrent grade III gliomas, which include
astrocytoma like Gracie's, and recurrent glioblastoma, a deadly grade IV brain tumor with a
mean survival of 14 months. Principal investigator Dr. Nicholas Butowski expects to enroll
up to 24 adults and anticipates that a trial for children will start once the adult study has
demonstrated safety.

"The goal of the trial is not a cure, but extended survival and higher quality of life during that
extended survival," Bankiewicz said. In many patients, quality of life is compromised not
only by the tumor but also by "systemic administration of powerful chemotherapy drugs and
radiation," he said.

Tumors that return after treatment may continue to be treated with this method, something
that cannot usually be done with other therapies, he said. "This technology holds promise that
we may be able to encapsulate in nano-particles drugs that when delivered locally might
target migrating tumor cells and suppress recurrences."

Helping humans

Progress in the human trial is an exciting step for Ziebe, who lost her beloved Gracie nine
months into the trial, but says her goal was to help people, too. In the end, the cause of death
was not brain tumor.

"After Gracie's last MRI, I got a call from Dr. Dickinson," she said. "The good news was that
she was beating the brain tumor. The bad news was that a new cancer had been found."

That new diagnosis was hemangiosarcoma, a virulent blood cancer that occurs in older dogs, 6/56/1/53/1130:1501:5A1
6/5/13 10:51 AM
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Courtesy Of Anita Ziebe

UC Davis' Dr. Peter Dickinson with Gracie, the first of 18 pet dogs whose tumors received a new
HealthPet dog with tturemaotrmpeionntetehreadt tmreaaytmpernotl-oSnagnpFeroanpclies'csolCivherso.nicle
http://www.sfchronicle.com/health/article/Pet-dog-with-tumor-pion...

Following a scan, Gracie had a biopsy to confirm her diagnosis of grade III astrocytoma, and
believed to be unrelated to her treatment. Gracie became withdrawn almost immediately,
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Pet dog with tumor pioneerededurtuhganiinzfeuGsiroancsiedaelfievwerdeadysdilraetecrt.ly to the tumor, via burr holes in the skull.
treatmentS"uGzraancniee Lloevigehditsoapflraeyelwanicthe wsqruiteear.kEy-mtoayisl:. [email protected] the trial. She had a

good appetite, didn't lose weight or seem sick. She showed no side effects or symptoms of the

tumor," said Ziebe, whose love for her canine companion prompted her to start a hospital pet

therapy program and become a certified dog trainer.

Gracie's tolerance of the treatment was fairly typical of the dogs, with no permanent side
effects noted - a finding that has caused a quiet commotion among brain tumor specialists at
UCSF.

Drugs to treat brain tumors in humans are typically taken orally or intravenously, but a major
challenge is that they do not cross the blood-brain barrier in sufficient quantities to attack the
tumor. Increasing dosage is not feasible because of systemic side effects, such as nausea,
vomiting and neutropenia, a condition in which a type of white blood cell plummets, making
the patient vulnerable to life-threatening infections.

© 2013 Hearst Communications Inc.

Bypassing a barrier

Bypassing this systemic route is one solution. About a decade ago Drs. Krystof Bankiewicz
and John Park of UCSF's department of neurological surgery embarked on a project using a
drug that would be toxic to the tumor and a delivery system that would be exquisitely targeted
to reach the tumor alone.

The upshot was CPT-11, an existing cancer drug called ironotecan that Park modified by
encapsulating it into oil droplets that would remain inactive until they reached their
destination. Bankiewicz developed a complex device in which a thin tube is inserted through
a port attached to the skull. The drug is injected through the tube, which is removed after
infusion. To maximize safety and efficacy, neurosurgeons track the drug's distribution
throughout the tumor in real time, via MRI.

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