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New Advances May Slow Tumor Growth In Pancreatic Cancer-(Yahoo
News-01/07/2005)
Making new strides in their ongoing effort
to understand mechanisms behind the relentless growth of cancer cells,
researchers at Dartmouth Medical School have found a promising key that
may open doors to future treatments in pancreatic and other forms of
cancer. The innovation lies in manipulating an overabundance of
chemo-resistant molecules in pancreatic cancer that inactivate pathways
that would normally suppress cell growth.
Published in the Journal of Biological Chemistry,
the study was led by Dr. Murray Korc, a pioneer in early research on
growth factor receptors in pancreatic cancer, and chair of the department
of medicine at Dartmouth Medical School (DMS) and Dartmouth-Hitchcock
Medical Center, and a member of the Norris Cotton Cancer Center. His
team's research has focused on suppressing pancreatic tumor growth by
determining the mechanisms that enable the cells to grow so quickly. "Pancreatic cancer is an incredibly resilient and aggressive disease,"
said Korc. "It grows quickly without causing symptoms, is resistant to
chemotherapy, has a strong tendency to metastasize, and patients are often
beyond surgery when it is diagnosed."
This study builds on the team's prior research on a molecule called
Smad7, found in half of all human pancreatic cancers. Smad7 lies in
pathways that normally play an important role in regulating cell growth
and often prevents cells when proliferating too quickly. But Smad7
interferes with these pathways that are normally regulated by TGF-beta
molecules, so they cannot regulate the growth of cells, and these cells
continue to grow unchecked until they eventually become tumors. "Previously, we found that Smad7 blocks the ability of TGF-beta to
inhibit the growth of these cancer cells," said study co-author Dr.
Nichole Boyer Arnold, a postdoctoral fellow at DMS and a member of the
Norris Cotton Cancer Center. "In this study, we discovered that Smad7 is
able to do this by suppressing the function of the retinoblastoma (RB)
protein." The RB protein is crucial to empowering TGF-beta to control cell
growth.
DMS researchers also found that pancreatic cancer cells generate TGF-beta
molecules at a much faster rate than normal. "It's a devilish mechanism,"
explains Korc. "Smad7 not only prevents TGF-beta molecules from slowing
the cancer down, but enables them to multiply at a high rate, and thus
gives the cancer another growth benefit. In addition, TGF-beta molecules
are still able to stimulate blood vessel formation and enhance the growth
of adjoining cells, which further increases the cancer's ability to
metastasize." Korc likens the process to a scorpion that not only has a newfound
immunity to his own poison, but every time he stings himself, he gets
bigger and more powerful.
"Now that we know how Smad7 is able to inactivate TGF-beta growth
suppressive effects by preventing RB from functioning properly, we can
focus our research on the RB protein," said Korc. They hope to find a way
to disrupt Smad7's ability to affect the RB protein in human pancreatic
cancers. Of the 31,000 people in the US that get pancreatic cancer this
year, 30,300 will die from it, according to Korc, and most patients die
within six months, which is why these advances in new therapies are so
important. He notes that even if his lab is able to overcome these problems in RB,
it will not lead to a "cure" for pancreatic cancer. Pancreatic patients
are under attack from so many different directions that the answer will
not lie in one particular aspect of therapy. The authors hope that their
work will add to a growing arsenal of treatments that, when combined in a
form of therapy individualized to each patient, will have an impact on
this devastating disease.
[Top]
Metal Stents Are Safe And Effective For Treatment Of Obstructions From
Pancreatic Cancer-(Yahoo News-05/05/2005)
One key goal of treating pancreatic cancer, which is
often fatal within a year, is making sure patients have a good quality of
life with as few complications as possible. This is especially important
if they are candidates for surgical removal of the cancer. Now, doctors at the University of Virginia Health System report that
placing self-expanding metal tubes or stents (covered with a synthetic
material) to drain the common bile duct is a safe and effective treatment
for a major complication of pancreatic cancer-- obstructive jaundice. This
type of jaundice occurs frequently when pancreatic tumors block the flow
of bile from the liver. Cancer patients can experience yellowing of the
skin and eyes, itching and dark urine. If untreated, jaundice can lead to
infection and abscesses in the liver, which can be fatal.
"It is important that we can now relieve these very significant
complications without the major surgery that can often lead to long-term
hospitalization and possibly death," said Dr. Michel Kahaleh, a
gastroenterologist and assistant professor of internal medicine at UVa's
Digestive Health Center of Excellence. "We can provide resolution of
jaundice and alleviate the symptoms for a long period of time, at least
long enough until patients are able to have their cancer treated with
surgery."
Between March 2001 and November 2004, UVa doctors inserted 88 stents
called covered Wallstents (manufactured by Boston Scientific, Inc.) in 80
patients at UVa with bile duct obstructions from malignant cancer. These
stents were developed to prevent the growth of tumors into the stent
itself and feature a metallic skeleton bound to a synthetic covering
resistant to bile and other gastric and pancreatic juices. Writing in the
April 2005 issue of the journal Gastrointestinal Endoscopy, Kahaleh and
his UVa colleagues report that the stents were still open in 90 percent of
the patients after three months and were open in almost 80 percent of
patients after one year. Complications, however, included migration
(movement) of the stent, occlusion of the stent and obstructions of the
cystic duct. The stents were easily removed and replaced where needed.
In an accompanying editorial in the same issue of Gastrointestinal
Endoscopy, Dr. David L. Carr-Locke of Harvard Medical School wrote that
covered metal stents to help palliate bile duct malignancy is "the
appropriate step in stent technology development and probably confers a
clinical advantage over its uncovered counterpart."
[Top]
New Drug Targets Pancreatic Cancer Two Ways-(HealthDayNews-29/01/2005)
A new drug that targets pancreatic cancer in
two ways is being tested by oncologists at the University of Southern
California/Norris Comprehensive Cancer Center. The Phase II clinical trial of 90 people with metastatic pancreatic
cancer will evaluate how well BAY 43-9006 works alone and when it's used
with gemcitabine, the current standard treatment for pancreatic cancer. It's believed that BAY 43-9006 disrupts cell signaling that's crucial to
the development of many cancers. The drug also appears to block the ability
of tumors to grow new blood vessels that they require for nourishment.
"Pancreatic cancer is a major health problem, because we do not yet have
highly effective ways to deal with it," principal investigator Dr.
Heinz-Josef Lenz, an associate professor of medicine at USC's Keck School of
Medicine, said in a prepared statement. "The cancer is difficult to diagnose early, when it is most treatable,
and can be aggressive. Because of the lack of effective systemic therapies,
only 1 percent to 4 percent of patients will be alive five years after
diagnosis," Lenz said. He said he hopes that targeted drugs such as BAY 43-9006 will prove an
effective part of first-line treatment for pancreatic cancer and help
patients respond better to chemotherapy.
Pancreatic cancer is diagnosed in more than 29,000 people each year in
the United States.
[Top]
Race a Factor in Pancreatic Cancer Surgery-(Reuters
Health-24/01/2005)
It's known that
African Americans have an elevated risk of pancreatic cancer, but new study
findings show they may also be less likely to receive surgery for the
disease. Researchers found that among more than 2,700 Californians diagnosed with
pancreatic cancer between 1988 and 1998, black patients were at slightly
higher risk of being diagnosed with advanced cancer. They were also less
likely than white, Hispanic or Asian patients to receive surgery, even when
the cancer was in an earlier stage. Dr. Kenneth J. Chang and his colleagues at the University of California,
Irvine, report the findings in the journal Cancer.
Overall, African Americans had the highest incidence of pancreatic cancer
of any racial group, a finding in line with past research, they note. It's
thought that this racial disparity may be related to higher rates of certain
pancreatic cancer risk factors among African Americans -- including smoking,
diabetes and obesity. Pancreatic cancer is among the most deadly of cancers because it
typically progresses quickly and is usually caught only at a later stage,
often after the cancer has spread to other organs.
Although the risk of being diagnosed at an advanced stage is high in
general, black patients in the current study were at somewhat greater risk
than other racial groups. Moreover, they were the least likely to have
surgery, even when the cancer was caught at an earlier stage, according to
Chang's team. Among patients with early-stage pancreatic cancer, 80 percent of black
patients did not receive surgery, compared with 77 percent of Asian
patients, 68 percent of whites and about 62 percent of Hispanics.
There are a few potential explanations for the discrepancy, according to
Chang and his colleagues. One factor could be tumor location; tumors in a
part of the pancreas known as the "head" are considered more amenable to
surgical removal. In this study, both black patients and Asian patients --
those with the second-lowest rate of surgery -- had fewer tumors in the head
of the pancreas. Another factor could be the aggressiveness of the cancer, according to
the researchers. A previous study found that African Americans had far
higher rates of a particular genetic mutation that may make some pancreatic
tumors especially aggressive. One factor that did not seem to play a role was health insurance. Rates
of medical coverage, Chang's team found, were comparable among the different
racial groups. More studies are needed, the researchers conclude, to "delineate the
barriers" black patients may face in receiving surgery for pancreatic
cancer.
[Top]
Smoking Further Linked to Deadly Pancreatic
Cancer-(Reuters-20/01/2005)
Smoking may speed the
growth of pancreatic cancer by causing it to develop in younger people, U.S.
researchers reported. The study, presented at a meeting of cancer specialists in Chicago, may
help doctors better understand a particularly deadly cancer, which kills
virtually all of its victims within a year. Dr. Randall Brand and colleagues at Northwestern University in Illinois
studied 18,346 pancreatic cancer patients treated between 1993 and 2003. The
patients, taken from a database of 350 hospitals around the country, all
gave smoking histories.
"Smoking appears to accelerate the onset of pancreatic cancer
development," Brand told a news conference. The median age for the patients was 73. But current smokers were
diagnosed at 63 -- a full 10 years sooner. People who had smoked in the past
and quit were diagnosed at age 70. Brand said other studies have indicated that smoking can affect both the
initial development and spread of cancer. "Since the age of diagnosis of previous smokers was younger than
nonsmokers, this suggests that smoking could impact upon the initiation
phase," Brand said.
In 2005, an estimated 32,180 people will be diagnosed with pancreatic
cancer, and 31,800 people will die from it, according to American Cancer
Society projections. It is the fourth leading cause of cancer death. "Since pancreatic cancer is almost uniformly fatal, a younger age of
onset means more potential years of life lost. Thus, these findings offer
yet another important reason for individuals not only to stop smoking, but
never to start," Brand said. Smoking also causes lung, esophageal and bladder cancer, among others.
A second study presented at the meeting of the American Society of
Clinical Oncology found that adding a new drug to standard chemotherapy for
pancreatic cancer gave some patients a few extra weeks of life. The new drug, erlotinib, is sold under the brand name Tarceva by
Genentech Inc. and OSI Pharmaceuticals Inc. and is one of a new generation
of targeted cancer drugs that affects a molecule used by tumor cells to
grow. For the study, half of a group of 569 pancreatic cancer patients got a
standard therapy, Eli Lilly & Co.'s gemcitabine or Gemzar, while the other
half got Gemzar plus Tarceva.
After a year, 24 percent of the patients who got Tarceva were alive,
compared to 17 percent of patients given Gemzar alone. "This is a difficult
disease to treat," said Dr. Malcolm Moore of Canada's National Cancer
Institute, who led the trial. "This is a bit of a light and gives us
some clues about how we can improve the treatment of this condition."
[Top]
Lorus
Therapeutics CEO says 2005 will be pivotal for cancer drug developer-(Yahoo
News-19/11/2004)
Next year will be a pivotal for Lorus
Therapeutics as the biotechnology developer makes preparations for
commericializing Virulizin, a treatment for pancreatic cancer, CEO Jim
Wright told shareholders Thursday. Lorus
has done much of the difficult work in its drug development programs and
brought them to a late stage in the necessary clinical research that is
needed to obtain regulatory approvals, Wright said at the company's annual
meeting. "Now we are putting in place the means to reap the rewards
of this considerable investment," he said. "We
are in a critical year as we prepare for the results from our pivotal
clinical trial of Virulizin and the advancement of our other technologies
in our broad, diverse product pipeline."
"When will we know if the drug is working? Well, I would say
approximately a year down the road," Wright said. He estimated Lorus
will end its clinical trials in mid-2005, take several more months to
analyse and compile the data, and submit its application for the FDA
approval of Virulizin as a commercial drug in late 2005 or early 2006.
Lorus already obtained fast-track status from the FDA, meaning the agency
will give Virulizin's application priority, reducing the time required for
the FDA approval process to about three to six months, he said. "If
we didn't have that, it would be up to a year. So that's a very valuable
thing we've obtained from the FDA," Wright said.
[Top]
Researchers
Find New Key In Pancreatic Cancer Cases-(Yahoo News- 09/11/2004)
It is the deadliest of all cancers, but
there is new hope in the battle against pancreatic cancer. NewsCenter 5's
Rhonda Mann reported that researchers in Worcester believe they're on the
verge of something big, and now family members of those lost to the
disease are asking for your help. "Karen was always healthy. She was
a big strong outgoing kid. All of a sudden, bang one day, and you have the
bad news," said Dick Sweeney. When doctors diagnosed Karen with
pancreatic cancer, she was three months pregnant. Miraculously, surgeons
carefully removed the tumor without disturbing the baby in the womb.
Months later, Adam was born healthy. But just
afterwards, the disease returned. Karen died just after Adam's first
birthday.
Researchers have had few clues to this
evasive cancer. It spreads quickly, producing almost no symptoms. "Within
six months, half of the people diagnosed with this disease will die and
within five years, 98 percent succumb to this disease," University of
Massachusetts Medical Center Dr. Ashok Saluia said. But
Saluja has found an important key -- Heat Shock Proteins. In times of
stress, they're released into the body to protect cells -- but they're
overly abundant in pancreatic cancer cases -- protecting tumor cells from
destruction. "Our initial studies
indicate that by inhibiting heat shock protein levels, HSP70 levels we can
kill the cells, kill the tumor cells," Saluja said. The
research is in its very earliest stages. But for a disease so deadly it is
providing some hope for the future.
Those like the Sweeneys are now asking for
donations for the research to continue. While pancreatic cancer is the
most deadly, it receives one-twelfth the funding of breast cancer.
"What can we do to make her life positive?
If we can fix it so someone else's child can live, that's what we'll do,"
Dick Sweeney said.
[Top]
Smoking,
Heredity Pose Pancreatic Cancer Risk-(HealthDay News-08/11/2004)
Smoking may be an environmental trigger that activates pancreatic
cancer in people with a family history of this usually fatal disease, a
new study suggests.
The finding underscores the importance of
not smoking if your family members have had pancreatic cancer. In
addition, you should consider being screened for the disease beginning at
around 40. About 10 percent to 15 percent of those with pancreatic cancer
have a family history of the disease.
"We found that patients with a
hereditary predisposition to pancreatic cancer tend to present at an
earlier age, compared with the general population of patients who have
pancreatic cancer," said lead researcher Dr. Ted James, a clinical
fellow at Roswell Park Cancer Institute. In addition, "The majority
of patients with familial pancreatic cancer were smokers."
In their study, James and his colleagues
collected data on 826 patients with pancreatic cancer. Among these, 30 had
a family history of pancreatic cancer, according to the report in the
November online edition of Cancer.
The data revealed the average age at
diagnosis of those with a family history of pancreatic cancer was 57.1
years, compared with 61 years for those without a family history.
Moreover, 36.7 percent of those with hereditary pancreatic cancer were
diagnosed before age 50, compared with 18.3 percent of those who had no
family history of this cancer.
James' team also found that 87 percent of
those with hereditary pancreatic cancer smoked, compared with 66 percent
of others with the disease.
There may be a different expression of
genes among people with a family history of pancreatic cancer, and smoking
may put them at a higher risk, James said.
"Unfortunately, survival from this
disease is pretty poor," James said. "Survival tends to be the
lowest, compared with other cancers. Anything we can do in terms of
prevention or early detection is going to have a great impact. Even with
its dismal prognoses, it is much better if you find it early, when you
have a better chance of survival, than if you find it in the later
stages."
James said that many are coming to the
conclusion that early screening with ultrasound is important for those
with a family history of pancreatic cancer.
"There may be a benefit in some sort
of screening program for these patients. Screening should begin around 40.
If you have a family history of pancreatic cancer, you may want to look
for screening programs," James said. "And obviously, if you
smoke, you should stop smoking, and if you are a nonsmoker, then stay
so."
"It's not just lung cancer," said
Dr. Herman Kattlove, a medical oncologist and spokesman for the American
Cancer Society. "Smoking is a cause of many cancers, and is a risk
factor for all pancreatic cancer."
Kattlove believes that those with a family
history of pancreatic cancer should be evaluated. "There is evidence
that if you catch them early you can cure them," he said.
[Top]
OSI
Jumps on Pancreatic Cancer Trial-(Reuters-20/09/2004)
Shares
of OSI Pharmaceuticals Inc. jumped 13 percent in pre-market trade after
the company's experimental drug was shown to prolong the lives of patients
with cancer of the pancreas. OSI is developing the pill,
called Tarceva, in partnership with Swiss drugmaker Roche and Genentech
Inc., a biotech company in which Roche holds a majority stake. The drug is
already awaiting U.S. and European approval for lung cancer following
favorable results of trials to treat that disease.
Wall Street had expected Tarceva
to generate potential annual sales of up to $1.6 billion by 2009 for
treatment of lung cancer, but analysts said the drug's sales potential is
now substantially higher because of additional promising use for
pancreatic cancer. Earlier on Monday, the three companies reported
favorable results from a late-stage trial of Tarceva among patients with
advanced pancreatic cancer. Those who took it along with a standard
treatment -- Eli Lilly and Co.'s Gemzar -- lived two weeks longer than
patients taking a placebo and Gemzar. The two additional weeks is a
statistically significant 23.5 percent extension of life. Those taking
Tarceva lived an average of 6.4 months, compared with 5.9 months for those
who did not take it. Although the difference is only about two weeks,
analysts said it was a meaningful advance against the difficult-to-treat
disease.
Genentech said new treatments for
pancreatic cancer are needed because only 20 percent of patients survive
one year after diagnosis. Besides showing effectiveness against pancreatic
cancer, one of the most difficult types of tumor to treat, analysts said
the results dispelled concerns about whether Tarceva can work well in
combination with other drugs. "No single therapy or combination has
shown any clinical benefit in pancreatic cancer since the arrival of (Eli)
Lilly's Gemzar eight years ago," DRKW analysts wrote.
Tarceva blocks a protein called
epidermal growth factor that is found in large numbers on the surface of
many types of cancer cells. ImClone Systems Inc. and Bristol-Myers Squibb
Co. sell a drug for colon cancer, Erbitux, that blocks the same protein,
but their drug must be injected.
[Top]
Research
finds cancer drug not effective as given-(Yahoo News-09/06/2004)
Jason
Fisher, an undergraduate engineering student at the University of Pittsburgh,
yesterday presented the results of his senior project in a seemingly unlikely
place: the annual meeting of the American Society of Clinical Oncology.
By approaching the bodies of cancer patients much as an engineer would
analyze the processes of a chemical plant, Fisher had shown that perhaps
half of a common chemotherapy drug, gemcitabine, is inactivated when administered
as recommended. Fisher presented his findings at the meeting in New Orleans,
where 28,000 cancer specialists have gathered. "It quantifies something
that people have been talking about for some time," said Dr. Merrill Egorin,
professor of medicine and pharmacology at the University of Pittsburgh
Cancer Institute.Fisher's
unusual presentation generated some "nice feedback," some of it from gemcitabine's
maker, Eli Lilly Co., said Egorin, who was a co-investigator on the study.
Gemcitabine
is widely used for treating pancreatic and lung cancers and generally
is administered as a 30-minute infusion. But some clinical evidence suggests
that the 30-minute infusion may overwhelm the body's ability to convert
the drug into an active form, Egorin said. A study at M.D. Anderson Cancer
Center in Houston that was published last year, for instance, showed that
the same dose administered at a slower rate for a longer time caused more
side effects, suggesting more of the drug was being activated. Fisher's
mathematical approach, based on what is known of gemcitabine's pharmacokinetic
characteristics and on blood tests from 31 patients in a federally sponsored
trial of gemcitabine, confirmed that the body can activate, on average,
only about half of the drug when it was administered in a 30-minute infusion.
Whether
that means the dosage could be halved -- potentially saving money -- or
whether the drug should be infused at a slower rate to improve the efficacy
of the therapy will still have to be determined in clinical studies, Egorin
noted. But the study shows how chemical engineering control theory, which
has been used in industrial settings for more than a half century, might
help physicians improve drug therapies, said Robert Parker, an assistant
professor of chemical engineering and Fisher's research advisor. It might
someday be possible not only to use these mathematical approaches to determine
the best general methods to administer a drug, but to use them to tailor
drug regimens to each patient, said Parker, whose own research focuses
on using control theory in the treatment of diabetes. "What they're trying
to do," Egorin said, "is treat the human body as a factory."
[Top]
Cell
Genesys reports initial data from GVAX pancreatic cancer vaccine programme-(Yahoo
News-30/06/2004)
Cell
Genesys Inc presented clinical data from an exploratory phase 2 clinical
trial of GVAX pancreatic cancer vaccine in patients with inoperable, metastatic
pancreatic cancer. The company also updated the status of a parallel phase
2 trial in patients with operable pancreatic cancer who receive the vaccine
after surgery, an approach which continues to be the focus of the company's
GVAX pancreatic cancer vaccine programme. These two trials were prompted
by encouraging results from an earlier phase 1 clinical trial in operable
patients which demonstrated prolonged, disease-free survival of at least
six years in three of eight patients treated at therapeutic dose levels.
The new findings were presented by Daniel Laheru, assistant professor
of medical oncology at Johns Hopkins Kimmel Cancer Centre, and colleagues,
at the annual meeting of the Lustgarten Foundation for Pancreatic Cancer
Research, which was sponsored by the American Association of Cancer Research
and held in San Francisco, CA.
The
phase 2 trial in patients with inoperable pancreatic cancer enrolled 50
patients, the majority of whom had failed at least two prior chemotherapy
regimens. Patients were divided into two cohorts, both receiving up to
six doses of GVAX pancreatic cancer vaccine at 21-day intervals. Cohort
A (30 patients) received GVAX pancreatic cancer vaccine alone, and cohort
B (20 patients) received GVAX pancreatic cancer vaccine in combination
with low-dose cyclophosphamide, a chemotherapeutic agent which has been
shown in the subtherapeutic doses administered to enhance the immune response
by reducing "suppressor" T lymphocyte function in the absence of a direct
anticancer effect. Despite the very advanced stage and extensive prior
chemotherapy in the majority of patients, there was a trend toward an
improved outcome with combination therapy in cohort B by all measures
of clinical activity. Forty per cent of patients in cohort B demonstrated
stable disease, compared with 16.7 per cent in cohort A. Moreover, the
median time to progression was 57 days in cohort B and 42 days in cohort
A, and median survival in cohort B was 4.3 months compared with 2.3 months
in cohort A. In addition, there was a correlation between survival and
the patients' post-vaccination blood level of GM-CSF produced by GVAX
pancreatic vaccine. Median survival was 5.3 months for patients above
the median peak level and 1.8 months for patients below that level (p=0.03).Treatment
with GVAX pancreatic cancer vaccine with or without cyclophosphamide was
generally well tolerated.
In
other news, the company reported the status of enrolment for the second
phase 2 trial in patients with operable pancreatic cancer who receive
the vaccine after surgical resection of their tumour and adjuvant radiation
chemotherapy. This study, which is being conducted at Johns Hopkins Kimmel
Cancer Centre, has enrolled more than 45 out of a projected 60 patients.
Enrolment is expected to be completed this year and preliminary data may
be available during 2005. "The results reported from our trial in inoperable
pancreatic cancer demonstrate the safety and feasibility of administering
GVAX pancreatic cancer vaccine in combination with low dose cyclophosphamide
chemotherapy and suggest that this combination may have enhanced clinical
activity even in patients with the most advanced stage of this highly
aggressive cancer," stated Joseph J Vallner, president and chief operating
officer of Cell Genesys. Pancreatic cancer is the fourth leading cause
of cancer death in the United States. According to the American Cancer
Society, in 2004, an estimated 31,860 Americans will be diagnosed with
pancreatic cancer and approximately 31,270 Americans will die from the
disease.
[Top]
Benefits
of Current Therapeutic Options for Pancreatic Cancer are Eclipsed by Their
Toxicity and Inconvenience in Advanced Stages of the Disease-(PRNewswire-14/06/2004)
Decision
Resources, Inc., one of the world's leading research and advisory firms
focusing on pharmaceutical and health care issues, finds that the benefits
of current therapeutic options for pancreatic cancer are eclipsed by their
toxicity and inconvenience, especially in advanced stages of the disease.
A related constraining factor is a lack of early diagnosis, most patients
are diagnosed at an advanced disease stage, so the benefits of treatment
are outweighed by their toxicities and inconvenience. The new Pharmacor
study entitled Pancreatic Cancer also finds that the launch of therapeutic
vaccines such as Aphton/ Aventis Pasteur's Gastrimmune and Lorus's Virulizin
will be the major market driver. "Gastrimmune will be the first therapeutic
vaccine to launch and will initially be used to treat unresectable, advanced
pancreatic cancer patients not fit enough to receive gemcitabine," said
Mohamed Muhsin, M.Sc., analyst at Decision Resources. "This use of Gastrimmune
will lead to a rise in the number of treated patients. Toward the end
of the first half of our study period, Gastrimmune and Virulizin will
be launched in combination with cytotoxic therapy; therefore, most patients,
regardless of whether they receive gemcitabine, will be treated with a
vaccine."
About
Pancreatic Cancer Pancreatic cancer is the fourth leading cause of cancer-related
mortality. Surgical resection remains the only potentially curative option.
However, resection alone is often insufficient: up to 85% of patients
suffer recurrent disease, and more than 85% of patients are diagnosed
at a stage of the disease that is too advanced for surgical intervention.
[Top]
Aspirin
not linked to Pancreatic Cancer-(Yahoo News-10/04/2004)
Researchers
from the American Cancer Society have found that taking aspirin neither
increases a person's risk of dying from pancreatic cancer, nor decreases
it. Their study, published in the latest issue of the Journal of the National
Cancer Institute (Vol. 96, No. 7: 524-528), is the largest yet to examine
the relationship between the common painkiller and pancreatic cancer,
the fourth leading cause of cancer death in the US. The finding could
provide some reassurance to people who take aspirin regularly, said lead
author Eric Jacobs, PhD, a senior epidemiologist with ACS . "[Our] results
… do not support an important effect of aspirin use on pancreatic cancer
mortality," he said. Because pancreatic cancer is almost always fatal,
the results would most likely be the same for incidence of pancreatic
cancer, he noted .
Previous
research on the issue has yielded mixed results. The Iowa Women's Health
Study, for instance, found that women who used aspirin frequently had
a lower risk of pancreatic cancer than women who didn't use aspirin. But
more recently, the Nurses' Health Study found that women who were long-term
aspirin users or who took 2 or more pills per week had a greater risk
of developing the disease. Although both of those studies included substantial
numbers of women (28,000 and 88,000, respectively), Jacobs noted that
the ACS study included many more people than either of them. He and his
colleagues studied 987,590 men and women for 18 years. The participants
were asked about their aspirin use and about other factors that could
influence their risk of pancreatic cancer, such as having diabetes, smoking,
and being overweight or obese. During the course of the study, 4,577 people
died of pancreatic cancer.
The
researchers found no associations between aspirin use and pancreatic cancer,
even after taking the other risk factors into account. People who used
aspirin daily were no more or less likely to die of pancreatic cancer
than those who used it only occasionally or those who never used it. The
results were the same for both men and women . The study did not examine
the dose of aspirin each person took, just how often it was taken. Millions
of Americans take aspirin daily because it is proven to reduce the risk
of heart disease. Many studies also suggest aspirin can reduce the risk
of colon cancer and possibly some other cancers. But there are currently
no recommendations to use aspirin to ward off cancer of any type.
"The
American Cancer Society does not recommend aspirin use for cancer prevention,
and these findings will not affect our recommendations," Jacobs said.
Because aspirin use can lead to serious side effects like stomach bleeding,
it is wise to consult a doctor before beginning any aspirin regimen .
About 31,270 people in the United States are expected to get pancreatic
cancer this year, according to ACS estimates, and most of them will die
from it. Survival is poor because the disease is very hard to detect in
its early stages. Tumors in the pancreas cannot be seen or felt during
routine physical examinations, and there are no reliable screening tests.
Patients rarely have any symptoms until the tumor has grown fairly large
or spread to other organs . Experts say exercising, eating right, and
not smoking are ways people can reduce their risk of developing pancreatic
cancer .
[Top]
IntrinsiQ
Research and WWMR Reinvent Oncology Market Intelligence-(PRNewswire-09/04/2004)
WWMR,
Inc. today announced that it has entered into a partnership with IntrinsiQ
Research to produce the definitive pancreatic cancer market intelligence
program, based heavily on IntrinsiQ's database, which uses real-time chemotherapy
data directly from oncology patients' medical records. Commenting on partnering
with IntrinsiQ Research, Inc., Susan Olsen, President of WWMR, Inc, stated,
"We have long been looking for a chemotherapy database with IntrinsiQ's
qualities. At last there is a data source that reports how cancer patients
are actually being treated. Since clinicians' real-time chemotherapy orders
are the database's building blocks, we are able to identify important
drug use habits and detect key drug use trends earlier in the commercial
cycle.
Access
to this data provides a vital dimension of insight into the treatment
of pancreatic cancer, and this program creates a new standard of reporting
on current and future oncology drug use in this emerging market." Mitchell
Daitz, President of IntrinsiQ Research commented, "Synergies between WWMR
and IntrinsiQ will result in new understandings of pancreatic cancer drug
use, today and into the future. We are excited to be partnering with WWMR,
given their expertise in oncology-related consulting and their track-record
in market analysis. At the heart of this venture is a leveraging of IntrinsiQ's
data with WWMR's demonstrated capabilities in reporting on current and
emerging pharmaceutical and biotech markets."
The
Pancreatic Cancer Program will be launched in June 2004, coinciding with
the annual conference of the American Society of Clinical Oncology (ASCO).
With the addition of rigorous analysis and commentary, the program will
deliver comprehensive market intelligence through product and market forecasts,
epidemiological data, treatment trends, and product pipeline evaluations.
Moreover, clinicians' opinions about unmet clinical needs and of specific
investigational agents will augment the review of the hard data. In addition,
periodic updates to the data and analysis will be delivered to clients
to ensure access to the latest information and trends occurring in the
marketplace.
[Top]
Nerve
Block Best for Pancreatic Cancer Pain-(Reuters Health-03/03/2004)
Blocking
certain sensory nerves is more effective than standard drug therapy at
relieving the severe pain seen with pancreatic cancer, according to research
conducted at the Mayo Clinic in Rochester, Minnesota. "Pancreatic cancer
is notorious for being associated with terrible pain" and patients usually
only survive a few months, Dr. Gilbert Y. Wong, a Mayo Clinic anesthesiologist
specializing in pain medicine, told Reuters Health. "In this study, we
confirmed our clinic experience that (the nerve) block may allow these
patients to live more comfortably, often for the remainder of their lives."
With
the nerve block, a needle is inserted into the back until it reaches a
nerve structure called the celiac ganglion. A concentrated alcohol solution
is then injected, which destroys nerves in the ganglion, effectively stopping
pancreatic pain signals from reaching the patient's spinal cord and brain.
In the new study, reported in the Journal of the American Medical Association,
Wong and colleagues randomly assigned 100 patients with pancreatic cancer
pain to receive either the nerve block or standard analgesic therapy.
All of the patients were followed until death or for at least one year
after enrolling in the study. During the first week, patients in both
groups reported less intense pain but patients receiving the block had
a significantly larger decrease from baseline in pain intensity than patients
receiving standard therapy. Moreover, follow-up through the first six
months showed that nerve block patients continued to have significantly
lower levels of pain than other patients.
"With
(nerve block), the injected substances destroy the nerve centers responsible
for pain transmission for the majority of upper abdominal...pain so the
effect can be potentially long lasting and that is in fact what we found,"
Wong noted. Quality of life also improved during the first week in both
arms, but gradually declined with time. Survival was not markedly different
between the two study arms. The findings of this study indicate that the
nerve block technique "should be considered a treatment option" for pancreatic
cancer pain, Wong said. "Other types of upper abdominal cancer-related
pain may potentially be amenable to this type of nerve block technique
as well," he added
[Top]
Pancreatic
Cancer Tied to Long-Term Aspirin Use-(HealthDayNews-06/01/2004)
Could
people who take aspirin for prolonged periods be putting themselves at
greater risk of pancreatic cancer? Maybe so, says a new study asking that
question of more than 88,000 nurses. Aspirin has long been thought to
suppress tumors of the digestive tract and other organs. And recent research
has found no evidence that aspirin users are more likely to suffer pancreatic
cancer, even offering hints the drug may protect the insulin-secreting
gland from tumors. But the latest work suggests that people who take the
drug consistently over a period of decades have a nearly 60 percent higher
risk of developing pancreatic cancer than those who take aspirin less
regularly. "It seems to be consistent use that counts," says study leader
Dr. Eva S. Schernhammer, a cancer researcher at Harvard Medical School
in Boston.
She
is quick to caution that while the study is the largest of its kind to
date, it turned up only 161 cases of pancreatic cancer among the entire
pool of volunteers over an 18-year period. "There is not much data available
to investigate such associations," says Schernhammer, whose findings appear
in the Jan. 7 issue of the Journal of the National Cancer Institute. Although
the evidence is murky, the researchers say their study suggests women
who took more aspirin each week over time increased their odds of developing
pancreatic cancer.
However,
that trend couldn't be confirmed with statistical certainty. The line
from aspirin to pancreatic cancer, if it exists, may run through obesity.
Not only were obese women more likely than their thinner peers to develop
the cancer while taking aspirin, but the heavier they were, the greater
their risk, Schernhammer says. "We did see that the effects in the overall
cohort seemed to be restricted to women who were more obese," she says.
Previous research has linked obesity with pancreatic tumors.Millions
of Americans take low doses of aspirin every day to prevent heart attacks
and strokes, problems that kill far more people each year than pancreatic
cancer. "Overall, the prevalence of cardiovascular disease is so much
higher than the prevalence of pancreatic cancer that the benefits would
probably still outweigh the risk," Schernhammer says.
Dr.
John Baron, an epidemiologist at Dartmouth Medical School and author of
an editorial accompanying the journal article, calls the findings "provocative"
and says they should force doctors "to think carefully about the actions
of aspirin and other [non-steroidal anti-inflammatory drugs] and the mechanisms
underlying pancreatic cancer." But Baron says the results may be misleading.
The research seems to suggest that, at least in some cases, pancreatic
tumors triggered aspirin use and not the other way around.
Kirsten
Moysich, an epidemiologist at the Roswell Park Cancer Institute in Buffalo,
N.Y., has looked at aspirin and various cancers, including pancreatic
tumors (she found no harm or benefit). In general, Moysich says, the drug
appears to protect against cancers, most notably in the colon and rectum,
and possibly the lung and breast. However, she says, contrary evidence
"shouldn't be ignored. We cannot make global public health recommendation
about regular aspirin use if we don't know the whole picture." And while
aspirin "seems to be a wonderful drug," it does have known side effects,
including a propensity to cause potentially serious gastric bleeding.
More than 29,000 Americans will be diagnosed with pancreatic cancer this
year, according to the National Cancer Institute. The disease is the nation's
fifth leading cancer killer, behind tumors of the lung, breast, colon
and rectum, and prostate gland.
[Top]
Daily
Aspirin Use Linked with Pancreatic Cancer-(ET-27/10/2003)
Women who take an aspirin a day -- which millions do to prevent heart
attack and stroke as well as to treat headaches -- may raise their risk
of getting deadly pancreatic cancer, U.S. researchers said. The surprising
finding worried doctors, who say women will now have to talk seriously
with their physicians about the risk of taking a daily aspirin. Pancreatic
cancer affects only 31,000 Americans a year, but it kills virtually all
its victims within three years. The study of 88,000 nurses found that
those who took two or more aspirins a week for 20 years or more had a
58 percent higher risk of pancreatic cancer. "Apart from smoking, this
one of the few risk factors that have been identified for pancreatic cancer,"
Dr. Eva Schernhammer of Harvard Medical School and Brigham and Women's
Hospital in Boston, who led the study, told a news conference. "Initially
we expected that aspirin would protect against pancreatic cancer, especially
since its preventive role in colorectal cancer has been well documented.
However, now it appears that we need to examine the relationship more
thoroughly," Schernhammer added in a statement. "This finding does not
mean that women should no longer use aspirin. There are still important
benefits to the drug; we also need other large cohort studies to confirm
our finding before we can draw any conclusions."
Schernhammer
and colleagues presented their findings to a meeting in Phoenix, Arizona,
of the American Association for Cancer Research. They studied 88,378 women
taking part in a large and wide-ranging study of nurses and their health.
Over 18 years, 161 of the nurses developed pancreatic cancer. Those who
took 14 tablets or more per week had an 86 percent greater risk of pancreatic
cancer than non-users. The nurses who took between six and 13 tablets
had a 41 percent higher risk, while those who only took one to three aspirins
a week had an 11 percent greater risk. The women who took the most aspirin
said they were taking it not to protect against heart disease, but because
of headaches or other aches and pains.
Even with the increased risk, heart disease is a much greater threat to
a woman's, or a man's, health. It is by far the biggest killer in the
United States and other developed nations. The
American Heart Association says cardiovascular disease killed more than
945,000 Americans in 2000. Doctors do not clearly understand what causes
pancreatic cancer, or what makes it so deadly. Obesity is another risk
factor, but Schernhammer said her team's findings held regardless of a
woman's weight, whether she smoked and whether she had diabetes. Schernhammer
noted that one study showed that regular aspirin use may cause pancreatitis
-- an inflammation of the pancreas that can sometimes lead to pancreatic
cancer. "There is urgent need to settle the biologic reasons for pancreatic
cancer," she said.
[Top]
Pancreatic
Cancer, Aspirin Link No Cause for Panic-(ET-30/10/2003)
Women
who take aspirin regularly should not panic about a recent study that
suggests long-term use could increase the risk of pancreatic cancer, the
study's author and other experts say. The findings would need to be confirmed
by other large, well-designed trials before doctors would consider changing
recommendations for aspirin use, said lead researcher Eva Schernhammer,
MD, of Harvard University Medical School. "No decisions have ever been
based on a single study," she noted. Even if these results are confirmed,
it might not affect recommendations for aspirin use because aspirin has
health benefits that may outweigh the risk of pancreatic cancer, said
Rick Alteri, MD, a medical editor with the American Cancer Society. Millions
of women (and men) in the United States take aspirin daily because it
has been proven to reduce the risk of heart disease, the leading killer
of American women. Studies also suggest that regular aspirin use may reduce
the risk of colorectal cancer, the third most common cancer in the US,
although there are currently no recommendations to take aspirin for this
purpose.
Schernhammer's study examined aspirin use among more than 88,000 women
who were taking part in the Nurses' Health Study, a long-term investigation
of risk factors for disease in women. It was presented at a meeting of
the American Association for Cancer Research; it has not yet been published
in a peer-reviewed journal. Schernhammer and her colleagues found that
women who took at least two regular aspirin tablets per week increased
their risk of developing pancreatic cancer. The risk rose as women took
more aspirins per week, and if they used aspirin over longer periods of
time. Over 18 years of follow-up, 161 women in the study developed cancer
of the pancreas.
This
isn't the first study to examine the relationship between aspirin and
pancreatic cancer. Some research has suggested aspirin could raise the
risk. But just last year, data from the Iowa Women's Health Study, another
large long-term trial, suggested aspirin actually protects against this
disease. Schernhammer said she and her colleagues had expected to confirm
the findings of the Iowa study, and were surprised to get a different
result. She noted, though, that the Iowa study did not assess aspirin
use as thoroughly as her study did. "You can't compare the two studies,
so we need more studies to compare associations, and those studies would
need to have similarly detailed information about aspirin use," she said.
In the meantime, should women stop taking aspirin? "No, definitely no,
for many reasons," Schernhammer said. For one thing, "the evidence just
isn't strong enough," she noted. But more importantly, she said, aspirin
has many benefits for preventing other diseases that are much more common
than pancreatic cancer.
Heart
disease, for instance, affects one out of every five men and women in
the United States, according to the American Heart Association. In 2000,
more than 500,000 women and more than 440,000 men died from some form
of heart disease. Colon cancer strikes more than 105,000 people each year,
and kills about 57,000. About 30,700 Americans get pancreatic cancer each
year, and about 30,000 die from it. The average woman's lifetime risk
of developing this disease is relatively low, about 1.24%. In this study,
taking at least two aspirins daily over 20 years raised that risk by 58%.
But even if this finding is confirmed, a woman's overall risk would still
be less than 2%. Other risk factors, like smoking and obesity, are far
more dangerous. Women who are concerned about pancreatic cancer should
speak to their doctors before they consider giving up aspirin, especially
if they are taking it to treat or prevent heart disease or some other
condition, said Alteri. Giving up cigarettes, eating right, and exercising
are more practical steps women can take to reduce their chances of developing
pancreatic cancer, Schernhammer said.
[Top]
First
Steps Towards a Vaccine for Pancreatic Cancer-(ET-25/09/2003)
Research
carried out in the United States has raised the hope that one day there
could be a vaccine against pancreatic cancer -- one of the most difficult
cancers to treat successfully. Dr Robert Maki told ECCO12 -- The European
Cancer Conference that preliminary work with a cancer vaccine created
from a heat-shock protein taken from the patient's own tumor had resulted
in one patient out of the ten vaccinated still alive and without disease
after five years, and two more alive and without disease after more than
two years. The typical survival after surgery for pancreas cancer is 14-15
months.
Heat-shock
proteins (HSPs) are made by genes in response to some form of stress on
a cell and help the cell rebuild itself after a potentially lethal attack.
HSPs work by sticking to and refolding damaged proteins back to their
normal structure. A tumor cell would have HSPs stuck to proteins specific
for the cancer, and a vaccine based on HSPs taken from the patient's tumor
would prompt the patient's immune system to attack cells containing the
proteins stuck to the HSPs wherever they were -- the greatest number of
that particular type of proteins being in the tumor itself -- thereby
killing the cancer. Dr Maki warned that patients should not get excited
about the results of this research, however, as it was too early to tell
whether it would be possible to create a vaccine that could be used on
all pancreatic cancer patients, and the patients involved in the trial
had been carefully selected and might have been ones that would have done
well anyway.
Dr Maki, an assistant member in the division of GI oncology in the department
of medicine, and co-director of the sarcoma programmed at the Memorial
Sloan-Kettering Cancer Center in New York, USA, told delegates that he
and his colleagues had run a phase I trial on 10 pancreatic patients using
a vaccine based on a heat-shock protein called HSPPC-96 taken from the
tumor of each patient (i.e. autologous). Initial problems in creating
the vaccine meant that the study was delayed half way through the study
to improve the vaccine-making process. Dr Maki said: "The problem is that
the pancreas makes digestive enzymes that destroy proteins . . . in other
words, the pancreatic tumor cells themselves can destroy the vaccine you
are trying to make, if you do not handle the tumor tissue carefully and
quickly. With improvement in the vaccine purification process, most patients
with the primary pancreatic cancer enrolled on the study were able to
receive vaccinations."
First,
surgeons operated to remove completely the primary tumor, and then the
patients were vaccinated within eight weeks of surgery. As far as doctors
could tell, the patients were disease-free at the time of their vaccinations.
None of the patients suffered side effects that limited the dose of the
vaccine, and none had chemotherapy or radiotherapy. Dr Maki said: "Tests
on the patients showed that at least some people we examined made a response
against the vaccine and therefore, hopefully, against the cancer. However,
we will only get a better picture of the efficacy of this vaccine when
we have the clinical results from a larger study." The overall survival
for the 10 patients was two and a half years, in comparison to 14.3 months,
the historical average. "Over 95% of people with pancreatic cancer die,
typically within two years of diagnosis, and mortality is still about
90% even for those who have complete removal of their pancreatic cancer.
So the finding of even a few patients surviving two years or more is promising
regarding the usefulness of this vaccine after removal of the cancer.
However, and this is a big however, we may be biased in who we selected
for the study. Only people who could have an operation were eligible;
we screened out people who had evidence of spread of tumor before they
entered the study. Perhaps, just by chance, we got a few people who were
destined to do well. So enthusiasm about any phase II study has to be
tempered by the fact that you need a proper randomized study to determine
the vaccine's usefulness," he said.
HSPPC-96
has been shown to have quite a dramatic effect in some patients with metastatic
melanoma and so Dr Maki hopes that trials could be run to further test
its efficacy against pancreatic cancer as well. In the meantime, until
a larger study has been run, it will not be known for certain whether
this vaccine has real potential against pancreatic cancer. Trials are
also underway to test the vaccine in the treatment of kidney cancer. The
story of this vaccine is a good example of how earlier discoveries at
the lab bench can eventually translate into potential new therapies for
patients. Dr Maki's PhD was based on cloning and purifying the human HSPCC-96
molecule. "It is nice to see that well over 10 years after my PhD, this
interesting molecule is undergoing examination in the clinic. It is gratifying
to see the studies move from the bench to patients, where I hope some
benefit will be seen. Similarly, this same technique could be used in
preparing vaccines against infectious diseases -- another very large area
of potential use for these vaccines."
[Top]
Fish
Oil Helps Cancer Patients-(HealthDayNews-10/09/2003)
Fish oil may help
prevent cachexia, the severe wasting and weight loss experienced by people
with some types of advanced cancer, says a British study in the current
issue of Gut. Cachexia, a result of changes in metabolism and loss of
appetite, is a major factor in the illness and death of patients with
advanced cancer. This study included 200 people with pancreatic cancer.
A high-calorie, high-protein supplement was given to 105 of the patients,
while 95 of them received an energy-dense, high-protein supplement enriched
with omega 3 essential fatty acid and vitamins E and C. Each group drank
480 milligrams a day for eight weeks. Omega 3 essential fatty acids are
found in fatty fish such as salmon and herring. Before the study, the
patients had lost about 17 percent of their body weight and were losing
more than 3 kilograms of weight a month. After eight weeks of taking the
supplements, weight loss had stopped in both groups. When they examined
the data more closely, the researchers found a direct and significant
association between the amount of weight and muscle bulk gained and the
amount of fish oil supplement consumed by patients. This association was
not found in the patients taking the supplement without the fish oil.
Patients taking the fish oil supplement also reported a much improved
quality of life. The authors write that further research is necessary
to confirm their findings. '
[Top]
Smoking
Ups Hereditary Pancreatic Cancer: Study-(Reuters Health-16/05/2003)
People with two or more family members with pancreatic cancer should
be encouraged to kick the habit as smoking may nearly quadruple their
odds of developing the disease, researchers report. Among people with
a family history of pancreatic cancer, smoking appears to increase the
risk of the disease even more in men and in people younger than age 50,
according to the results of a new study. Pancreatic cancer is the fourth
leading cause of cancer deaths in the U.S. An estimated 30,000 people
will be diagnosed with the disease in 2003.
Most
people with pancreatic cancer do not have a family history of the illness,
but about 10 percent of pancreatic cancer cases are hereditary, according
to a report published in the journal Gastroenterology. Little is known
about what factors might play a role in tumor formation in familial, or
hereditary, pancreatic cancer, according to a team led by Dr. Stephen
J. Rulyak of the University of Washington in Seattle. Previously, researchers
identified a number of environmental factors, including smoking, that
may increase the risk for non-familial pancreatic cancer, but such effects
have not been evaluated for pancreatic cancer that runs in families, the
authors report. To investigate, Rulyak's team evaluated risk factors for
pancreatic cancer among 251 individuals from 28 families. All families
had at least two members with pancreatic cancer. Smoking was an independent
risk factor for familial pancreatic cancer, with smokers being almost
four times more likely to develop the disease than nonsmokers, the authors
report. The risk was increased about five times in male smokers and more
than seven times in smokers younger than 50. In addition, the researchers
found that smokers developed cancer almost a decade earlier than nonsmokers
-- at an average age of 59.6 years versus 69.1 years.
The
researchers also found that the risk of cancer increased with the number
of close relatives -- mother, father, sister or brother -- who had the
disease. For each first-degree relative with pancreatic cancer, the risk
rose by 40 percent. Although the pancreas produces the sugar-processing
hormone insulin, diabetes was not a risk factor for pancreatic cancer,
according to the report. "Overall, our results further highlight the dangers
of cigarette smoking and emphasize the need for additional research focusing
on gene-environment interactions in the genesis of pancreatic cancer,"
the authors conclude. The study received financial support from the National
Institutes of Health (news - web sites), the C.D. Smithers Foundation,
Solvay Pharmaceuticals, Inc. and the Italian Association for Cancer Research.
[Top]
Faulty
Gene May Contribute to Pancreatic Cancer-HealthScoutNews-04/02/03)
Mutations
in the BRCA2 gene, already known to increase the risk of breast and ovarian
cancers, may also make people susceptible to a hereditary form of pancreatic
cancer, German researchers conclude. Their findings echo those of previous
studies. "We have found mutations which are likely to explain in a subgroup
of families with pancreatic cancer cases why the disease occurs," says
Dr. Stephan A. Hahn, a professor of oncology at the Knappschafts-krankenhaus
University of Bochum in Bochum, Germany. Hahn is also co-author of the
new study, which appears in the Journal of the National Cancer Institute.
Hahn
and his colleagues identified 26 European families with at least two first-degree
relatives -- a sister or father, for instance -- with pancreatic cancer.
After testing them, the researchers found that 19 percent of the families
had at least one member who had either a mutation or a variant of BRCA2.
While the new research confirms findings in previous studies, including
one done by Johns Hopkins University researchers, Hahn says the study
population for his study is broader. Taken together, the studies "make
a strong case that a certain percent of familial pancreatic cancer is
likely caused by BRCA2 mutations," Hahn says. Exactly why is not known,
he adds.
The
pancreas, a six-inch gland located deep in the abdomen between the stomach
and the spine, makes insulin to help the body's cells use the sugar brought
to them by the blood, and makes digestive chemicals that help break down
food. In the United States, pancreatic cancer kills about 29,000 persons
a year, according to the National Cancer Institute, making it the fifth-leading
cause of cancer deaths. A genetic counselor at the UCLA Jonsson Comprehensive
Cancer Center in Los Angeles calls the new study "important," and says
it is a welcome contribution to the body of knowledge about pancreatic
cancer, which remains a puzzle to cancer experts. "We don't know that
much about pancreatic cancer," says Joyce Seldon, a certified genetic
counselor.
Men
are more likely than women to get pancreatic cancer, and cigarette smokers
have two to three times the risk of nonsmokers, according to the National
Cancer Institute. Diabetics are also more likely to get it. And about
10 percent of pancreatic cancer patients may have an inherited form of
the disease, Hahn says. "What this study is breaking ground on is the
association between BRCA2 and pancreatic cancer," Seldon says. "What the
actual risks are is not yet known."
What
should people do at this point? Hahn says if a family has "familial pancreatic
cancer" -- defined as families with at least two first-degree relatives
with pancreatic cancer -- members should seek information from a specialized
center that has genetics counselors on staff. "It's hard to tell them
how much of a risk [they have]," Hahn says. "Proper counseling is important,"
adds Gloria Petersen, a research scientist and professor of epidemiology
at the Mayo Clinic in Rochester, Minn., who co-authored an editorial accompanying
the study. "But we also recommend [getting it from] a research setting
at this time." Those who may already know they have the BRCA 2 mutation
should not be alarmed, Seldon says. "We know [from the research] the risk
[of pancreatic cancer for those with BRCA2 is higher than the general
population. How much higher, I don't think we know," she says.
[Top]
Gene
Therapy Fights Pancreatic Cancer in Mice-(Reuters Health-06/12/2002)
Because
it is often caught only in its more advanced stages, pancreatic cancer--the
fifth leading cause of cancer death in the US--is rarely curable. But
Japanese researchers are using gene therapy to achieve what they call
"dramatic" results in shrinking pancreatic tumors in mice, even after
the cancer has spread beyond the pancreas. Treatments like these targeted
to specific cancer-causing genes "offer some hope for developing a novel
approach to pancreatic cancer," write Dr. Masaru Oonuma and colleagues
at Tohoku University Graduate School of Medicine in Sendai, Japan. They
report their findings in a recent issue of the International Journal of
Cancer.
Pancreatic
cancer is most often a "silent killer," with no symptoms appearing until
the malignancy has become very advanced. Surgery at this point is often
out of the question, and drug therapy has limited success because pancreatic
cancer cells are notoriously resistant to even the most powerful chemotherapy.
One way to short-circuit drug resistance may be to target genes within
cancer cells that help the cell dodge these medications. In their study,
Oonuma's team first injected human-derived pancreatic cancer cells into
mice. When the pancreatic cancer had spread beyond the pancreas itself
into surrounding tissues, the researchers infected some of the mice with
a harmless virus that also "piggybacked" a compound called uracil phosphoribosyl
transferase (UPRT) to the area of malignancy. According to the researchers,
UPRT effectively "switches on" a gene that works to overcome a cancer
cell's resistance to chemotherapy.
In
fact, mice treated with a combination of gene therapy plus the powerful
cancer drug 5-fluorouracil (5FU) "showed a dramatic tumor reduction without
adverse effects," Oonuma and his colleagues report. Tumor shrinkage occurred
both within the mouse pancreas and in the areas beyond the organ, while
leaving normal tissues unharmed. Encouraged by their success, the Japanese
team is conducting similar experiments in mice affected with human-derived
liver tumors, as well. And they note that a human trial, using a very
similar approach, is already under way in patients with head and neck
cancers. Although much work needs to be done, and routine use of these
types of therapies in the hospital setting is still years away, Oonuma
and his colleagues call their gene therapy approach "a promising tool
for targeting (metastatic) pancreatic cancer."
[Top]
Starchy
Diet Linked to Pancreatic Cancer (Reuters-03/09/2002)
A diet high in white
bread, white rice and potatoes puts women at much higher risk of pancreatic
cancer--especially if they are overweight and do not exercise much, researchers
reported. The finding, published in this week's Journal of the National
Cancer Institute, adds to research that links a "junk food" diet with
a higher risk of certain cancers. Previously, the only known risk factor
for pancreatic cancer, which kills 30,000 people a year in the United
States, was smoking. "The take-home message for women who are overweight
and sedentary is that a diet high in starchy foods may increase their
risk of pancreatic cancer," Dr. Charles Fuchs of the Dana-Farber Cancer
Institute, Brigham and Women's Hospital and the Harvard School of Public
Health in Boston, who led the study, said in a statement. "Substituting
less starchy vegetables such as broccoli for potatoes and rice and snacking
on fruit are some simple steps they can take to reduce this potentially
serious health risk."
Fuchs and colleagues
used data from the Nurse's Health Study, an ongoing study of 89,000 nurses
who carefully record their diet and other habits and whose health is then
watched. They found that eating lots of unrefined starches, such as white
bread and potatoes, increased the risk of pancreatic cancer by 57%--but
the numbers were just on the border of being statistically significant,
meaning the link is not a strong one. However, Fuchs said some of the
nurses were at a much higher risk. "If you took women who were both overweight
and sedentary, their risk was 2.5 times higher," he said in a telephone
interview.
There is a good reason
to suspect diet may be involved in pancreatic cancer, Fuchs said. "Our
presumption is that all these things--being obese, a sedentary lifestyle,
a diet high in sugars--all increase insulin levels," he said. Insulin
production is one of the pancreas' main functions. "In the laboratory,
insulin promotes the growth of pancreatic cancer cells. We suspect that
body states that maintain high levels of insulin increase pancreatic cancer's
ability to survive and grow." Insulin is used by the body to process blood
sugar. Researchers now believe that up to a third of all cancers may be
caused by diet and lifestyle. The obvious link is between smoking and
lung cancer, but diets high in some fats and perhaps red meat have been
associated with colon and breast cancer, for instance.
The American Institute
for Cancer Research promotes eating a diet high in vegetables, fruit and
whole grains to prevent cancer, as well as getting plenty of exercise.
Pancreatic cancer is an especially deadly cancer, killing all but about
5% of patients within five years. It is difficult to study because 80%
of patients have an advanced stage of the cancer when they are diagnosed.
"The principle symptom of pancreatic cancer is profound weight loss--which
lowers levels of the key hormones involved," Fuchs said. By then, other
genes and chromosomes in the cells have become mutated and the cancer
is out of control. This finding may help people avoid developing the cancer
and may eventually lead to better treatments, Fuchs said. And individuals
living on typical Western diets should try to eat fewer processed grains
and white potatoes anyway, he added. "There are good reasons to avoid
diets that are rich in these foods because they are not only associated
in this cohort with pancreatic cancer--they are also associated with and
increased risk of cardiovascular disease, heart disease and diabetes,"
he said.
[Top]
Aspirin
May Ward Off Pancreas Cancer (Associated Press -06/08/2002)
Aspirin, already
widely used by people hoping to ward off a heart attack, may also be helpful
in preventing pancreatic cancer. In recent years reports of the benefits
of aspirin have increased, including modest reductions in the polyps that
can lead to colon cancer. Now, University of Minnesota researchers report
an apparent association between taking aspirin and reducing rates of often-deadly
pancreatic cancer by as much as 43 percent. Their findings are reported
in the Journal of the National Cancer Institute
"This is an intriguing
study, more along the lines of hypothesis generating as opposed to testing,"
said Dr. Ernest Hawk of the National Cancer Institute, who was not part
of the research group. "I think that aspirin may very well have this sort
of activity but I wouldn't consider it definitive that this point," he
said. "They will have to work out the risks and benefits." Hawk noted
that this was an observational study, not a randomized, controlled trial.
"It provides information that needs to be tested in a controlled study,"
he said. There have been prior studies of pancreatic cancer that didn't
see any statistical effect in aspirin use, Hawk added. Because aspirin
can also have side effects, he said that people may not want to run out
and start taking it just on the basis of this study, but added that "researchers
may want to run out and do (more) studies."
The research team,
led by Kristin E. Anderson and Dr. Aaron R. Folsom, studied the use of
aspirin and other nonsteroidal anti-inflammatory drugs by 28,283 postmenopausal
women who responded to health questionnaires in the Iowa Women's Health
Study from 1992 to 1999. Women who took aspirin had a 43 percent lower
rate of pancreatic cancer than nonusers and the risk of the cancer declined
with increasing frequency of aspirin use, the team reported. Of 80 cases
of pancreatic cancer found in the study, 33 were women who never used
aspirin and 27 used it less than once a week. There were 10 cases among
women who took aspirin two to five times a week and 10 among those using
it six times or more weekly. Risk factors for pancreatic cancer are not
known and it is often rapidly fatal with few treatment options.
[Top]
Fatty
Diet Ups Pancreatic Cancer Risk in Smokers-(Reuters Health-14/05/2002)
Male smokers who
consume diets rich in saturated fat may be at increased risk of pancreatic
cancer, researchers report. Their study findings suggest that dietary
changes can help to lower the risk of pancreatic cancer, a disease in
which fewer than 5% of patients live for 5 years after diagnosis. Until
the tumor grows large, there are no symptoms, and the cancer usually spreads
to the lymph nodes, liver or lungs before it can be detected. "Diet is
a potentially modifiable factor in the prevention of pancreatic cancer,
and modification of diet may particularly benefit smokers, who are at
higher risk of the disease," according to Dr. Rachael Z. Stolzenberg-Solomon
from the National Cancer Institute in Bethesda, Maryland and colleagues.
Researchers have
long known that smoking and diet can raise the risk of pancreatic cancer,
but foods that boost the risk have been largely unknown. To investigate,
the researchers reviewed information on more than 27,000 male smokers
aged 50 to 69 who were enrolled in a study in Finland. Men who developed
pancreatic cancer had higher intakes of butter and saturated fat and lower
intakes of carbohydrates and total calories, compared with men who did
not develop pancreatic cancer. Men who consumed the highest amounts of
saturated fat were 60% more likely to be diagnosed with pancreatic cancer,
and men who consumed the greatest amount of butter were 40% more likely
to be diagnosed the disease over the next 12 years, the report indicates.
Men who consumed the most calories and carbohydrates were the least likely
to be diagnosed with pancreatic cancer, the researchers report in the
May issue of the American Journal of Epidemiology. Although the study
did not investigate how saturated fat might increase the risk of pancreatic
cancer among smokers, the authors point out that saturated fats are more
likely to be stored in the body as fat than other nutrients, and are used
less efficiently as energy. "These unique aspects of energy obtained from
fat may account for its cancer-promoting effects," Stolzenberg-Solomon
and colleagues write. Alternatively, fat and saturated fat may decrease
insulin sensitivity, which is a risk factor for diabetes. Previous research
has shown an association between pancreatic cancer and diabetes.
[Top]
Statins
Might Fight Spread of Pancreatic Cancer (Reuters Health-29/03/2002)
Statins,
a family of drugs that lower cholesterol, might also have a role in the
treatment of pancreatic cancer, Japanese researchers report. Pancreatic
cancer typically has a poor prognosis, with less than 1% of patients living
for 5 years after diagnosis. Until the tumor grows large, there are no
symptoms, and the cancer usually spreads to the lymph nodes, liver or
lungs before it can be detected.
The
Japanese team discovered, in a study of mice, that the spread of pancreatic
cancer cells to the liver was significantly reduced by a statin called
Lescol (fluvastatin). Only 10 of 12 mice (83%) treated with Lescol developed
liver cancer, versus 100% of 9 untreated mice. Even when Lescol-treated
mice did develop cancerous liver nodules, they had an average of 6, versus
25 in the untreated mice. The mice started receiving Lescol before they
had cancer. But a second set of experiments showed that Lescol was also
effective when mice were treated after pancreatic cancer had spread to
the liver, a scenario more likely to occur in humans. The research team,
led by Dr. Toshiyuki Kusama, published its findings in a recent issue
of the medical journal Gastroenterology.
Why
should a drug that lowers cholesterol also stop the spread of cancer?
Statins reduce cholesterol levels because they block an enzyme called
HMG-CoA, which the liver needs to form cholesterol. The scientists showed
in a laboratory experiment that HMG-CoA has another role in the body:
it is necessary for proper functioning of epidermal growth factor, a substance
that helps pancreatic cancer cells invade other organs and grow into tumors.
In
a commentary, Dr. Roland Schmid of the University of Ulm, Germany, suggests
that statins might be a useful add-on therapy for pancreatic cancer patients
after surgery. But he expresses doubt that statins alone would be helpful,
because pancreatic cancer would be well established before treatment started.
In
an interview with Reuters Health, Kusama agreed, but pointed out that
in a previous animal study by other scientists, a statin called Zocor
(simvastatin) enhanced the effect of cancer chemotherapy. "It might be
worth testing the combined use of a statin and chemotherapeutic agents"
in patients who have advanced pancreatic cancer that has spread to the
liver, according to Kusama, who is a biochemist at the Osaka Medical Center
for Cancer and Cardiovascular Diseases.
Much
more study is needed before statins can be recommended as anticancer drugs,
Kusama cautioned. Still, the Japanese team points out that a statin called
Pravachol (pravastatin) prolonged survival in patients with one type of
liver cancer. And Schmid reports that in laboratory studies, statins have
been able to kill some types of cancer cells directly, and there is evidence
that they block formation of the blood vessels that feed tumor growth.
Perhaps
one day some individuals will take a statin simply for prevention of cancer,
Schmid comments. He notes that in one drug trial, patients taking a statin
were 28% less likely to develop cancer than patients who did not. The
study was not designed expressly for the purpose of looking at the anticancer
effect of statins, so other research would be needed to confirm the finding,
but "this approach might be worth pursuing," Schmid concludes.
[Top]
Light
Therapy Prolongs Life in Pancreatic Cancer-(Health Scout News-13/03/2002)
Aiming
laser light at chemically sensitized pancreatic tumors could be the key
to prolonging life among people with this disease. British researchers
report that photodynamic therapy (PDT), in which laser light is delivered
directly to cancer cells treated with a photosensitizing drug, significantly
improved survival times among a small group of patients with pancreatic
cancer. This is the first report of using PDT to treat pancreatic cancer,
and the researchers say the increased survival time points to important
clinical implications for the therapy. The findings appear in the journal
Gut.
The
pancreas is a glandular organ behind the stomach that produces enzymes
and hormones, including insulin. Dr. Norman Marcon, director of the University
of Toronto's Therapeutic Endoscopy Program, says that while it's difficult
to say whether one cancer is worse than another, "[pancreatic cancer]
is one of the worst ones to have from the point of view of survival."
Every year, roughly 30,300 Americans develop pancreatic cancer, and roughly
29,700 will die of the disease, largely because they have no symptoms
until the cancer is advanced. Those grim statistics make finding a new
approach to therapy all the more desirable.
Lead
investigator Dr. Stephen Bown, director of the National Medical Laser
Center in London, describes PDT as light producing a chemical effect.
"Basically, it's a new way of producing local areas of tissue destruction
using a combination of a photosensitizing drug and laser light," says
Bown. "There's no heat involved, so it's not like most lasers, and there's
no ionizing radiation, so it's not like radiotherapy. The reason it's
so attractive is that it kills living cells but does not damage the scaffolding
that holds tissue together."
This
means that while it destroys the cancerous cells growing in the pancreas,
it leaves the connective tissue that forms the basis of the organ's structure
intact, allowing non-cancerous cells to regrow in place of the destroyed
tumor. After testing the therapy on rats and hamsters, the researchers
determined the tissues surrounding the pancreas could tolerate PDT. Their
next step was to study the effect of the therapy in humans with pancreatic
cancer.
Bown
and his colleagues enrolled 16 patients between the ages of 46 and 77
with cancer isolated in one region of the pancreas. Before the experiment,
all of the patients required a biliary stent procedure to relieve jaundice,
a common symptom of pancreatic cancer. The photosensitizing drug meso-tetrahydroxyphenyl
chlorin (mTHPC) was delivered intravenously to the patients, who were
then kept in a darkened room for three days to allow the drug to spread
and to avoid light reactions.
At
that time, each patient was sedated and up to six needles were placed
into the deepest part of the tumor. A diode laser inserted through the
needles into the tumor delivered red light directly into the tumor. "Where
the light hits, the tumor undergoes necrosis [death]. The mechanism is
something called singlet oxygen -- it releases a very localized, short-lived
toxin which usually works by destroying the blood supply of the tumor,"
he explains.
Three
patients with progressive pancreatic cancer underwent chemotherapy after
the procedure. All of the patients eventually died of the cancer, but
they lived longer. While Bown says the typical patient with localized
pancreatic cancer has roughly a 20 percent chance of surviving for one
year after surgery, 44 percent of the patients treated in this study were
alive one year after the light therapy. Two patients lived for over two
years, and one survived for 31 months before succumbing to the disease.
After
the procedure, each patient was closely followed in the hospital and after
discharge, and returned for monitoring of the tumor. Two patients developed
intestinal bleeding that required surgery, 15 of the patients experienced
some pain at the site of the drug injection, five patients developed diarrhea
that responded to therapy and all 16 developed some skin sensitivity to
light. Some patients had more than one symptom.
Marcon
adds that normal pancreas cells are uniquely resistant to the damaging
effects of PDT, which is crucial given the functional importance of the
pancreas gland. "This treatment was pretty well tolerated, and we could
produce destruction of quite a large area of the cancer. The real art
in the future is to know exactly how far the tissue destruction will go,
and we've still got a lot of research [to do] to refine that." He says
future studies should compare PDT to chemotherapy.
[Top]
Heredity's
Role in Pancreatic Cancer Confirmed-(Reuters Health-08/03/2002)
A
study of people with a family history of pancreatic cancer shows them
to be at increased risk of developing the disease, according to Canadian
researchers. Dr. Steven A. Narod of the University of Toronto and his
colleagues suggest that these first-degree relatives of patients with
pancreatic cancer, who are themselves at high risk for the disease, "might
benefit from increased surveillance or chemoprevention. We are now starting
a project on ultrasound screening for men and women at high risk. Pancreatic
cancer is a highly fatal disease, and we must also concentrate our efforts
on better means of prevention."
Currently,
most people diagnosed with pancreatic cancer will die within a year of
detection, largely because the disease is rarely caught before it has
spread. The organ is located deep within the abdomen, and early pancreatic
cancer often produces no clear symptoms.
Narod
and his colleagues conducted a study of 174 patients with pancreatic cancer
and 136 healthy ("control") individuals. The results were published in
the International Journal of Cancer. There were 150 cases of all types
of cancer in first-degree relatives of those with pancreatic cancer and
122 such cases in controls. But relatives of the pancreatic cancer patients
were nearly five times more likely to have pancreatic cancer than the
relatives of healthy patients. About 9% of relatives of the patients had
the cancer, versus roughly 2% of the healthy individuals' relatives.
Overall,
the lifetime risk of pancreatic cancer was 4.7% for first-degree relatives
of those with pancreatic cancer. Relatives of patients who were diagnosed
with pancreatic cancer before age 60 had a 7.2% chance of developing the
disease themselves. This rose to 12.3% in first-degree relatives of patients
with multiple cancers, the report indicates.
[Top]
Chemo
helps treat pancreatic cancer-(Times of India Online-12/11/2001)
Chemotherapy
after surgery can help to prolong the lives of patients suffering from
pancreatic cancer, according to a study published recently. Cancer of
the pancreas, a gland in the abdomen that is an important part of the
digestive system, is one of the most deadly and difficult cancers to treat.
Less than 10 percent of patients survive a year after they are diagnosed
with the disease. But new research published in the Lancet medical
journal shows that patients given chemotherapy after surgery survive 40
percent longer than other patients.
"For
too long, there has been a perception among clinicians that this is a
cancer too serious to do much about. Research is changing that and at
last we can give a glimmer of hope to patients," Professor John Neoptolemos,
of the Royal Liverpool University Hospital in northern England, said in
a statement.
In
a trial of 541 people with pancreatic cancer, patients who received after
surgery the drug 5-Fluorouracil, which is widely used to treat bowel cancer,
lived an average of six months longer than those who didn't. Neoptolemos
hopes that a new drug called Gemcitabine will extend survival rates even
further. "We are hopeful that the new drug will offer even better survival
to patients but we need a trial on this scale to confirm this," he added.
Cancer
of the pancreas is one of the 10 most common cancers. The pancreas makes
enzymes essential for digestion and produces insulin needed to regulate
blood sugars. "The disease is particularly hard to treat because it is
unusually aggressive, symptoms are often vague and appear at a late stage,
and surgery is very difficult," said Professor Nick Lemoine of the Imperial
Cancer Research Fund, a leading British charity.
The
disease occurs most often in people aged between 60 and 80. Symptoms include
weight loss, lack of appetite as well as stomach and back pain. Obese
people have a much higher risk of developing pancreatic cancer but a study
published earlier this year in the Journal of the American Medical Association
showed that moderate exercise can reduce the chance of getting the disease.
Walking or hiking as little as 1-1/2 hours per week was shown to reduce
the risk by 50 percent in obese people. But exercise did not appear to
have any effect on risk among participants in the study who were not overweight.
[Top]
Family
history, smoking up pancreatic cancer risk-(Times of India Online-29/04/01)
Having a close relative
with cancer of the pancreas significantly increases an individual's chance
of developing the disease, especially if that person smokes, researchers
report.
Previous studies that
looked at factors associated with pancreatic cancer have consistently
identified only increasing age and smoking as major risks.
The present study
interviewed 247 patients with cancer of the pancreas and 420 people without
cancer to determine whether any of their parents or siblings also had
the disease.
Having a close relative
with pancreatic cancer increased one's chance of developing the disease
by 2.5 times. And the risk was much higher for those individuals who not
only had a family member with pancreatic cancer, but who also smoked.
Their risk, the researchers found, was six times higher than that faced
by people without these two risk factors. In addition, the risk grew to
eightfold higher if the relative had developed pancreatic cancer before
age 60.
This study is the
first to suggest that the age of onset of pancreatic cancer in close relatives
is an important contributing risk factor of pancreatic cancer in people
who smoke. Abstinence from smoking is therefore even more important for
individuals in families with a history of pancreatic cancer.
[Top]
Folate
may shield smokers from pancreatic cancer -(Times of India Online-13/04/2001)
For older male smokers,
taking in more of the B vitamin folate-in food, rather than as supplements-appears
to reduce the risk of pancreatic cancer, a new study suggests. In a group
of more than 27,000 men aged 59 and 60 years, those who ate the most folate
had about half the risk of developing cancer of those who consumed the
least. A total of 157 men in the study developed pancreatic cancer. All
had completed food questionnaires as part of the study.
Pancreatic cancer
is the fifth leading killer among cancers in the United States. The authors
note that the World Cancer Research Fund and the American Institute for
Cancer Research recently reported that from 30% to 50% of cases of pancreatic
cancer are related to diet, although scientists are still not clear which
foods may promote the cancer and which might protect against it. According
to the American Cancer Society, cigarette smoking and a high-fat diet
both increase pancreatic cancer risk. The researchers found, consistent
with past research, that smoking nearly doubled pancreatic cancer risk.
The results of this
study are believed to be applicable to women as well since metabolism
of folate is not gender-related. Further studies are needed to determine
if the observed protective association between dietary folate and pancreatic
cancer reflects a cause-and-effect relation. The US Department of Agriculture
recommends that all adults eat five to nine servings of fruit and vegetables
a day, enough to cover the recommended 400 daily micrograms of folate.
Other folate-rich foods include orange juice, dried beans and peas and
fortified cereals.
[Top]
Irofulven
Holds Promise In Pancreatic Cancer In Patients Refractory to Gemzar (Gemcitabine)-(Cancer
Info-24/11/2000)
Results from a Phase
II clinical trial of irofulven, a novel anti-cancer agent being developed
by Mgi Pharma, Inc., demonstrated anti-tumor activity in patients with
advanced pancreatic cancer who were refractory to Gemzar (gemcitabine),
the current first-line chemotherapy approved for treatment of pancreatic
cancer. Results showed that ten of the 53 patients enrolled in the study
achieved six-month survival, the primary endpoint for the trial. Equally
important, two patients demonstrated objective responses; one patient
experienced tumor shrinkage of 100 percent and another patient experienced
an 84 percent decrease in tumor mass.
Enrollment is expected
to begin near year-end in a pivotal, Phase 3 trial with irofulven in advanced
pancreatic cancer patients who are refractory to gemcitabine chemotherapy,
following finalization of a protocol that will be based upon further discussion
with the United States Food and Drug Administration (FDA). Together with
the greatly improved tolerance recently reported from a dose optimization
trial and encouraging discussions with the FDA, the path for conducting
a pancreatic cancer registration trial with irofulven is clearly understood
and patient enrollment should begin soon.
Irofulven was administered
to patients with inoperable, advanced pancreatic cancer who were refractory
to gemcitabine therapy using a treatment cycle of five-minute intravenous
infusions each day for five days, which was repeated every 28 days. The
most common side effects included nausea, vomiting, fatigue and bone marrow
suppression. Patients in the planned pivotal, Phase III trial will be
randomized to irofulven or 5-flourouracil, the current salvage treatment
for advanced pancreatic cancer patients. They will receive irofulven using
the new every other week dosing schedule. In a recent dose optimization
trial, this schedule demonstrated greatly improved tolerance at equivalent
dose intensity in comparison to earlier dosing schedules. Median survival
will be the primary endpoint in the Phase III trial, with objective tumor
response and other clinical benefit measures as secondary endpoints. When
concluded, results from that trial are expected to become part of a new
drug application for filing with the FDA.
According to the American
Cancer Society, an estimated 28,300 new cases of pancreatic cancer will
be diagnosed in the United States this year, with 28,200 expected deaths.
Cancer of the pancreas generally occurs without symptoms until it is in
advanced stages and it has generally been considered a chemotherapy resistant
disease. For all stages combined, the five-year relative survival rate
is only four percent. Even modest improvements in clinical benefit are
considered to be important advances because pancreatic cancer is such
a devastating disease.
Data that further
expands the understanding of irofulven's mechanism of action is also presented.
In earlier studies it has been shown that irofulven inhibits DNA synthesis,
arrests the cell cycle in S phase and induces tumor selective apoptosis.
In the studies presented at the symposium, it was demonstrated that: (a)
very high levels of the anti-apoptotic protein Bcl-2 do not completely
block apoptotic tumor cell death caused by irofulven, (b) pro-apoptotic
effects of irofulven are likely to reflect its covalent binding to DNA
(death signaling pathway) and to cellular proteins (distortion of the
redox balance) and (c) irofulven produced a concentration-dependent inhibition
of cell growth in certain telomerase-positive cell lines and inhibition
of telomerase activity.
[Top]
Pesticides linked to pancreatic cancer - (Medivision-1-15
January)
High blood levels
of organochlorines, which were once used as pesticides, have been linked
to gene mutations found in patients with cancer of the pancreas. The study
is the first to link a genetic alteration commonly found in pancreatic
cancer patients and an environmental substance.
Current blood levels
of organochlorines probably reflect exposure to pesticides in the environment
over the past decade. Despite restriction in their use in Spain since
mid-1980s, recent surveys revealed their presence in 78-100 % of meat
samples and PCB in 50% of fish samples
[Top]
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