Pancreatic cancer procedures:

Pancreatic carcinoma is cancer of the
pancreas.
A tumor or cancer in the pancreas may
often grow without any symptoms at
first. This may mean pancreatic cancer
is more advanced when it is first found.



NEW URINE TEST FOR PANCREATIC
CANCER
A new urine test to diagnose
pancreatic cancer is being developed
by researchers at the Institute of
Cancer at Barts and The London
Hospital.
The test works by looking for raised
levels of a protein associated with
tumors and provides a diagnosis within
two hours.
Pancreatic cancer is one of the most
lethal forms of the disease, as it has
few symptoms in the early stages. It is
not usually picked up until patients
complain of abdominal pain and are
referred for scans - by which time it's
often very advanced.

PHOTODYNAMIC THERAPY USED IN
PANCREATIC CANCER TREATMENT
This is a very experimental treatment
involving a drug activated by light. We
do not know yet how much this might
help people with cancer of the
pancreas.
There is a small trial in London of
photodynamic therapy with a drug
called verteporfin. This trial is only
open to people who cannot have an
operation to remove their cancer. They
have the drug injected into a vein.
After the drug has had time to circulate
through the body and get into the
tumor, the doctor puts fibres through
the skin and into the area of the tumor.
The doctor guides the fibres into place
using an ultrasound or a CT scan to
make sure they are in position. Then a
laser light is shone directly into the
pancreas. The light activates the drug,
which kills the cancer cells.
After the treatment the patient must
stay out of direct sunlight for 2 days
because the skin may be very
sensitive.


OVERVIEW

PANCREATIC CANCER TREATMENT
ADVANCES

Pancreatic cancer is a quiet,
deadly disease.
According to the National Cancer
Institute, in 2010, in the US about
43,000 people was diagnosed and
just under 6,000 will survive.
Often, symptoms are not present
until very late, when it has spread
to other areas and surgical
removal is impossible.
Those who are  diagnosed early
have about a 22.5 percent five-
year survival rate compared to
those with late-stage disease at
the time of diagnosis who have a
less than 2 percent five-year
survival.
Visibility for the disease is already
on the rise due to recent celebrity
victims, including Apple's Steve
Jobs and Hollywood actor Patrick
Swayze.
Patrick Swayze was diagnosed with
stage IV pancreatic cancer that
had already spread to the liver in
March  2008 and lost his battle with
the disease in September 2009 at
the age of 57.
Steve Jobs, co-founder and chief
executive of Apple Inc.,  was
diagnosed with this rare, slow-
growing pancreatic tumor in 2004.
He reportedly underwent
'Whipple's procedure' (technically,
called a pancreatico-
duodenectomy) – meaning removal
of the pancreas and part of the
duodenum in July 2004 after
initially rejecting conventional
medical intervention.
The area surrounding pancreatic
cancers is very dense, fibrotic,
and hostile. This is one of the main
reasons standard therapies for
this disease often work so poorly.

To date, there are no screening
tests available to  the general
population.
Pancreatic cancer is dangerous to
screen for. The pancreas is
extremely sensitive--biopsies can
lead to potentially fatal
complications--but with few
symptoms, the cancer is usually
detected too late.


ACTIVATING THE IMMUNE SYSTEM:  
NOVEL TREATMENT AT PENN STATE
Researchers at the University of
Pennsylvania's Abramson Cancer
Center have discovered a novel
way of treating pancreatic cancer
by activating the immune system to
destroy the cancer's scaffolding.
The strategy was tested in a small
cohort of patients with advanced
pancreatic cancer, several of
whose tumors shrank substantially.
The results, published in the
March 25 2011  issue of Science.
"Until this research, we thought
the immune system needed to
attack the cancer directly in order
to be effective," said senior author
Robert H. Vonderheide, MD. "Now
we know that isn't necessarily so."
"Attacking the dense tissues
surrounding the cancer is another
approach, similar to attacking a
brick wall by dissolving the mortar
in the wall. Ultimately, the immune
system was able to eat away at this
tissue surrounding the cancer,
and the tumors fell apart as a
result of that assault. These
results provide fresh insight to
build new immune therapies for
cancer."
In the clinical trial led at Penn
pancreatic cancer patients
received standard gemcitabine
chemotherapy with an
experimental antibody
manufactured by Pfizer
Corporation. The antibody binds
and stimulates a cell surface
receptor called CD40, which is a
key regulator of T-cell activation.
The team initially hypothesized that
the CD40 antibodies would turn on
the T cells and allow them to attack
the tumor.
The treatment appeared to work,
with some patients' tumors
shrinking substantially and the
vast majority of tumors losing
metabolic activity after therapy,
although all of the responding
patients eventually relapsed.
When the researchers looked at
post-treatment tumor samples,
obtained via biopsy or surgical
removal, there were no T cells to
be seen. Instead, they saw an
abundance of another white blood
cell known as macrophages.
To understand what was
happening in the tissues of these
patients, Vonderheide and Beatty
and colleagues turned to a mouse
model of pancreatic cancer
developed several years ago at
Penn. Unlike older mouse models
that were simplistic models of
human disease, new genetically
engineered mice develop
spontaneous cancers that are very
close reproductions of human
tumors. "We can perform
preclinical trials in these mice with
the same principles we use in our
patients," Vonderheide says,
noting that the team even used a
randomization protocol to assign
individual mice to different arms of
the study.
When the investigators treated
mice that developed pancreatic
cancer with gemcitabine in
combination with CD40 antibodies,
the results looked like those of the
human trial. Some mouse tumors
shrank and were found to be
loaded with macrophages but
contained few or no T cells. Closer
inspection showed that the
macrophages were attacking what
is known as the tumor stroma, the
supporting tissue around the
tumor. Pancreatic tumors secrete
chemical signals that draw
macrophages to the tumor site, but
if left to their own devices, these
macrophages would protect the
tumor. However, treating the mice
(or patients) with CD40 antibodies
seemed to flip that system on its
head. "It is something of a Trojan
horse approach," Vonderheide
says. "The tumor is still calling in
macrophages, but now we've used
the CD40 receptor to re-educate
those macrophages to attack – not
promote – the tumor."
This clinical trial has been
completed (NCT00711191)


The current finding comes on the
heels of another, separate report
issued earlier this year by a
French-American team of
researchers (led by Dr. James Yao
of the University of Texas M.D.
Anderson Cancer Center), which
indicated that two growth-factor
inhibiting drugs (everolimus and
sunitinib) more than doubled
survival among patients
diagnosed with pancreatic
neuroendocrine tumors.



NEW DRUGS IN DEVELOPMENT
In advanced clinical development  
are the following products:
In Phase 3:
Abraxine, a  chemo from Celgene
and Abraxame. Abraxane is chemo,
paclitaxel protein-bound particles
for injectable suspension.  
It increased survival as a   the first-
line treatment of patients with
advanced pancreatic cancer in
Phase  1 and 2 trials. In 44 patients
treated at the recommended dose
of 125 mg/m2 Abraxane plus
gemcitabine [1000 mg/m2], the
median overall survival time was
12.2 months, an impressive
doubling of survival compared to
historical control of gemcitabine
administered alone

Afinitor, a signal transduction
inhibitor from Novartis.

Apple cofounder and CEO Steve
Jobs is on Novartis' Afinitor
treatment. Afinitor is used to treat
patients with advanced pancreatic
NET—neuroedocrine tumors that
cannot be removed through
surgery or has metastasized. In its
advanced stage, where
approximately 60 percent are
diagnosed, a five-year survival is
27 percent. With Afinitor, the first
new treatment in nearly 30 years,
tumor growth and progression are
significantly delayed.

In June 2010 Novartis reported
that its RADIANT-3 Phase 3 study of
Afinitor  (everolimus), plus best
supportive care met its primary
endpoint, showing that the drug
more than doubled median
progression-free survival,  or time
without tumor growth, from 4.6 to
11.0 months when compared with
placebo in patients with advanced
tumor.

And these are in Phase 2:
AMG 479, a monoclonal antibody
from Amgen. Amgen is developing
AMG 479,  a human monoclonal
antibody.
It   targets type 1 insulin-like
growth factor receptor [IGF-1R],
which plays an important role in
the regulation of cell growth and
survival.
From a Phase 2 study Amgen
reported  that the addition of AMG
479 to gemcitabine resulted in an
overall survival rate at six months
of 57% versus 50% with
gemcitabine alone and 39% versus
23% at 12 months.

TH-302, a chemo from Threshold
pharma. Threshold's   hypoxia-
activated prodrug, TH-302, in
combination with gemcitabine in
thirty-four patients with advanced
pancreatic cancer had one patient
with a complete response and 8
patients had a partial response.

Reolysin, a reovirus from
Oncolytics
GI-4000, a targeted molecular
immunotherapy from Celgene
PCI-27483, a signal tansduction
inhibitor from Pharmacyclics
GVAX Pancreas vaccine from
Biosate Pharma


.
POSSIBLE ACTION:

For information about treatments
and clinical trials for pancreatic
and other types of cancer at Penn,
please call 1-800-789-7366.

ONCOLINK: Visit OncoLinks Clinical
Trials Matching Service to see if
you match to a pancreatic trial at
Penn or one being conducted
elsewhere.