New drug may hold answer to cancer
Posted on: 08/25/2002
Sunday August 18, 2002 Page A11
New drug may hold answer to cancer
Clinical trials of Reolysin show promise
David Heyman, Calgary Herald
The calls come once … twice… up to six times a day. Occasionally,
people even walk into the renovation-filled Kensington offices with
its fresh paint on the walls and rolled-up carpet in the dusty
These callers know the Clary based company is testing a new cancer
treatment called Reolysin, which shows breathtaking promise in
clinical trials. But they don't have time to wait for Health Canada's
They are dying of cancer, or know someone who is, and they're
desperate for a cure. Most are amateur cancer experts, as up to date
on the latest research as many researchers thanks to the Internet,
and they're naturally pulled by hope toward the light of a cure.
Their questions are the same: When will Reolysin be available and can
they join the clinical trials?
The answer they get is simple, hard but frank: Reolysin (pronounced
REE-oh-LYE-sin) is unproven and years away from doctors' offices in
any event. And unless you meet certain strict requirements, you can't
join the trials.
On caller recently phoned Oncolytic' CEO Brad Thompson in tears,
accusing him of killing his cancer-stricken mother because he
wouldn't allow her to have and injection. When recalling the
conversation, he just shrugs because there was nothing he could do.
"If you have cancer today, the fact we've got this product doesn't
mean very much," say Thompson. "We're working for people who don't
have cancer yet."
It's not that he's unsympathetic. Thompson himself had a melanoma
removed from his right thigh in 1999, an event that not only changed
his life but also his career. Oncolytics phoned him looking for a CEO
that same year. He was busy at the time as CEO of Synsorb, another
Biotech company, and didn't often take such calls. But the idea of
running a company whose purpose was to win the battle against the
deadly disease held a special attraction.
"If I didn't have cancer, I doubt very much I'd be talking to you
today," says Thompson, who quickly convinced Synsorb to buy his
pursuer. Soon after, he left his post to concentrate on Oncolytics,
and now claims he's the third-lowest-paid CEO of a publicly traded
biotech company in Canada (though he won't reveal his salary).
Yet Thompson says he's willing to put off compensation because
Reolysin has shown tremendous, perhaps unprecedented, promise in
initial studies. Reolysin is composed of the reovirus, a naturally
occurring virus to which most people will have been exposed sometime
in their lives. Thanks to research headed by Patrick Lee at the
University of Calgary, it has been shown to kill cancer cells that
have an active Ras pathway while leaving normal cells healthy.
The Ras protein is a key regulator of cell growth. In some cancer
cells it mutates, causing uncontrolled growth and eventually cancer.
Up to two-thirds of cancers depend on mutated or active Ras pathways.
That means Reolysin could theoretically be used to treat up to two
thirds of all human cancers.
In research published last year in the Journal of the National Cancer
Institute, 20 of 23 mice given a single reovirus injection had their
tumours disappear completely.
Results of a Phase I human study – to determine only if Reolysin is
toxic – showed patients suffered no serious side-effects regardless
of the size of the dosage. They also saw that, when injected into
living humans, it can kill many kind of cancer cells including
breast, prostate, pancreas and brain tumours.
Oncolytics has now started a Phase II prostate cancer study, with 45
patients across Canada, along with the Phase I and II recurrent brain
caner study. Results for the brain cancer study will be released no
later than July 2003.
Still, much more work need to be done, and Health Canada approval is
The only people with access to Reolysin so far are those included in
the clinical trials, like Joan Lisoway, 57, the world's first brain
cancer patient to get the drug. The mother of two was diagnosed with
recurrent malignant glioma, one of the most aggressive and deadly
brain cancers, in February 1999. She was initially told few patients
in her condition live more than five years, with many dying much
sooner. And if word weren't enough, the MRI image of her tumour
explained it clearly.
"We didn't know anything about MRIs, but we could tell it wasn't
good." Says Lisoway's husband, Jim.
Five operations later, surgical assaults on her tumour have slowed
her voice along with her mental acuity but her eyes sparkle and her
smile charms those around her, as does the delicate strength with
which she copes with he condition.
"You just have to accept it." Says Joan Lisoway, whose daughter,
Deborah, is studying cellular biology at the University of Calgary
and did a recent paper on the reovirus.
"You're thankful for the time you're given."
Jim, as effervescent as his wife, says he's grateful for life's small
mercies. After working at Park's Canada for 33 years, he took a buy-
out package in 1998, just a few months before his wife's first
seizure. Although he initially had other ideas for filling his days,
he suddenly had plenty of time to take on his new role as caregiver.
"The good Lord looks after us sometimes, he says, adding the couple's
Christian faith has only strengthened over the years.
Ironically, the don't go often to St. Stephen's Anglican Church where
they were married 36 years ago because so many people want to help.
"If Joan was to walk in on a Sunday she'd be swamped by little old
ladies who have known her for years," says Jim.
Instead, the couple prefers to spend their days more quietly in the
backyard under the wooden gazebo reading the newspaper of gardening,
although they venture out at least once a day for coffee or a meal.
They also try their best to share their optimism with others in the
same situation. While waiting for their next appointment in the Tom
Baker Cancer Centre, they often take a moment to cheer up others in
the waiting room, telling them they're in good hands.
"These people are the best of the best," Jim says of the doctors in
Since Joan had the three injections of Reolysin into her brain tumour
June 27, hardly a week has done by without some kind of visit to a
doctor for an examination and blood test.
Doctors are fascinated to know how the treatment – based on the
action of the reovirus that seeks out and kills cancer cells while
leaving healthy ones alone – will work in humans.
In Joan, it appears to be working well so far, but few details are
available. Oncolytics is looking to have up to 37 other patients like
her try the treatment.
The question of how well Reolysin will work is still open, but
doctors involved in the trials are delighted to have a new tool in
the fight, especially for brain cancer.
For the last 30 to 40 years, improvements in conventional treatments
for brain cancer have utterly failed to extend patients' lives for
very long, says Dr. Peter Forsyth, a Calgary neurosurgeon who is
directing the clinical trials. Surgery, chemotherapy and radiation
remain comparatively ineffective for brain cancer compared with
diseases like leukemia, whose victims are usually cured.
"The reality is the majority of patients with glioblastoma die within
a year," says Forsyth.
Not only are current treatments often unable to help, they can do
tremendous damage by themselves.
Radiation, for example, is extremely toxic. "We do it because it's
the best we have," says Forsyth. "You balance something that's
incredibly toxic with something that's lethal."
Mark Hamilton, a neurosurgeon and head of pediatric neurosurgery at
the Children's Hospital, is the man who actually inject the Reolysin
into patients. He is virtually despondent with the range of options
he has available, especially when it comes to children.
"If you put radiation into a child under the age of three, you're
basically taking 30 IQ points away form them," he says. "It can be
None of the current treatments really get the entire tumour, he says.
Hamilton has even done hemispherectomies – removal of half of
someone's brain – but the fast spreading disease still comes back.
"You can't take it all out," he says. "If you leave one cell, it
Reolysin is at the very least, a new idea. It gives people in
Hamilton's position a chance to tell patients science is working on a
"We're moving into a new box," he says.
With the reovirus, it seems to track down and kill cancer cells
through the body in up to two-thirds of all cancers.
"It's extremely promising in test-tube animals," says Forsyth, who
worked with Lee in the lab to develop Reolysin.
"We're able to cure the animals we treat and the animals remain
healthy," says Forsyth. "To have something that works without a
single side-effect is astonishing. On the other hand, it's easier to
cure cancer in mice."
Other treatments have succeeded in mice, but failed in humans because
they've been proven to be too harmful, too ineffective or otherwise
useless, says Forsyth. Reolysin appears to work equally well, so far.
The bonus is, unlike other viruses being tested for the same purpose,
such as herpes or the common cold, it doesn't have apparent side-
effects and need not be altered before injection.
The reovirus, by contrast, is naturally harmless to humans. It was
this quality which led to its original use at the University of
Calgary, says Coffey. It can be studied by scientific novices in
detail but if it is accidentally spilled or inhaled, on need only
bring out a mop and pail rather than a biohazard suit. "It doesn't
kill grad students," he quips.
Coffey, on of the three names on the original reovirus patent, is now
employed by Oncolytics as vice president. His job is to talk with
doctors to help them understand the product. A native of Medicine
Hat, he moved to Calgary in 1989 and got his BSc in cell biology at
the University of Calgary. He did his doctoral thesis on the
Coffey and his colleagues are pushing for Reolysin's approval as hard
as they can. In fact, they've chosen brain cancer for their Phase I
and II trials because it usually kills quickly, so the effectiveness
will be noticeable comparatively quickly. And, with its active Ras
pathway, it's theoretically highly susceptible to Reolysin.
"We're doing it quickly. We all want it to go quicker," says Coffey.
"The product's potential is so huge."
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