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Avastin shows promise in brain cancer (UPI - 14/12/2007)
A clinical study in Michigan found that brain cancer patients treated with the drug Avastin are living longer without further progression of the disease.
The randomized Phase II study at Henry Ford Hospital in Detroit focused on patients with glioblastoma multiforme whose cancer had recurred after first- or second-line therapy. More than one-third who were treated with Avastin alone -- as well as more than half of those treated with Avastin in combination with the chemotherapy drug irinotecan -- lived for six months without further progression of the disease."This is very encouraging news," Dr. Tom Mikkelsen, co-director of the Hermelin Brain Tumor Center, said Friday in a release. "Historical estimates suggest that only 15 percent of patients with this aggressive type of brain cancer live without their cancer progressing within six months."
Avastin acts as an anti-angiogenesis agent that chokes off the blood supply to tumors, which in turn inhibits their growth and metastasis, the report said.
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Genentech's Avastin Drug Slows Down Brain Cancer (Correct) (Yahoo News- 18/11/2007)
(Corrects reference to brain cancer deaths in third paragraph of story originally published Nov. 18 to remove implied endorsement of the product.)
Genentech Inc., the largest U.S. maker of cancer drugs, said its Avastin medicine slowed the spread of brain tumors in a study, offering a potential option against a disease that has resisted therapy for 25 years.
About 36 percent of patients with relapsed brain cancer who took Avastin had their tumors remain stable for six months, according to research presented at the Society for Neuro-Oncology meeting today in Dallas. About 15 percent did that well on other drugs in previous studies, researchers said.
Avastin, approved for colon and lung tumors, is the company's second-biggest seller with $1.75 billion in sales in 2006. The medicine, which cuts off blood supply to tumors, is being tested in 300 clinical trials worldwide against 20 different types of cancer, Genentech said. An estimated 12,740 patients are expected to die of brain cancer this year, according to the American Cancer Society.
``These findings exceeded our expectations,'' said Hal Barron, Genentech's senior vice president of development, in a statement.
Genentech rose 46 cents to $74.99 on Nov. 16 in New York Stock Exchange composite trading. The stock has dropped 7.6 percent this year, underperforming a 7.9 percent gain in the Amex Biotech Index.
Phase II Results
The results come from the second of three phases of study normally required for regulatory approval. Researchers enrolled 167 patients with a relapsed form of glioblastoma, an aggressive form of brain cancer, who took Avastin or a combination of the drug and a chemotherapy agent,
irinotecan. Patients did even better on the combination, with 51 percent alive with stable tumors after six months.
``The findings suggested that at 6 months, more patients had lived without their cancer advancing when Avastin was administered as a single agent, or in combination with chemotherapy, than what we would normally expect,'' said Timothy Cloughesy, director of the Neuro-Oncology program at the Jonsson Comprehensive Cancer Center of the University of California, Los Angeles.
Genentech, based in South San Francisco, sponsored the study. The company plans to discuss the results with the U.S. Food and Drug Administration to determine next steps, said Genentech spokeswoman Kristina Becker, in a telephone interview.
Glioblastoma has proven notoriously difficult to treat. Newly diagnosed patients usually get chemotherapy, and once they relapse, they are expected to live about three to six months, according to previously published research. The five-year survival rate, 3 percent, hasn't changed for 25 years, according to the American Cancer Society.
Survival Data Next
Data on whether Avastin helped patients live longer is expected to be available in 2008, Becker said.
Side effects in the trial were consistent with other studies of Avastin, Becker said. About 8 percent of patients on Avastin had significant high blood pressure, and 6 percent had convulsions, the company said in a statement.
The findings confirmed an earlier study of 35 patients at Duke University, which found that 46 percent lived six months with stable tumors when taking Avastin. The study was published in the Journal of Clinical Oncology.
Genentech is majority-owned by Basel, Switzerland-based Roche Holding AG.
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Brain
cancer linked to nerve agent-(USA TODAY-25/07/2005)
For the first time, a study has found an increase in
brain cancer deaths among Gulf War veterans who might have been exposed to
the nerve agent sarin by the destruction of Iraqi weapons in 1991. About
100,000 of the 350,000 Army soldiers in the Persian Gulf could have been
exposed to sarin after soldiers blew up two large ammunition caches in
Khamisiyah, Iraq, in March 1991, according to a study commissioned by the
military and performed by the Institute of Medicine. The institute advises
the government on health policy.
According to the study, soldiers inside the "hazard
area" were about twice as likely as those outside it to die from brain
cancer. Because the actual number of brain cancer cases was small, the
overall mortality rate was the same for veterans in the hazard area and
outside the area, according to the study, published in the American
Journal of Public Health. Among unexposed soldiers, researchers found a brain
cancer death rate of 12 per 100,000 from 1991 to 2000, says William Page,
director of the study. Over the same period, researchers found 25 brain
cancer deaths per 100,000 veterans who were exposed. "It's a doubling of risk, but it's still a pretty
small risk," says Page, a senior program officer at the Institute of
Medicine.
The study did not address "Gulf War syndrome," as
some have called the collection of ailments experienced by returning
veterans. It examined whether soldiers possibly exposed to the destruction
of Iraqi weapons were more likely to die for any reason. They also singled
out specific diseases: breathing problems, infections, circulatory problems,
digestive ailments, accidents and suicides, as well as four types of cancer. The study's authors note that sarin has never been
shown to cause cancer. Page suggests that researchers follow veterans to see
whether the risk of brain cancer, which is believed to develop over 10 to 20
years, changes over time. Page also notes that the study doesn't prove that
being in the hazard area caused brain cancer.
Melissa Bondy, a professor of epidemiology at M.D.
Anderson Cancer Center in Houston, questions why only one or two days of
exposure would increase brain cancer mortality. Other experts note that the
study could shed light on the causes of brain tumors, about which doctors
know little.
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Study Says Brain Cancer Treatments Vary-(Yahoo
News-01/02/2005)
Brain cancer
in adults is a dreaded diagnosis with few established treatment guidelines,
resulting in wide variations in care that can make things even worse for
some patients, a study suggests. Nearly half of patients surveyed received
no chemotherapy despite evidence that it can boost survival. Anti-seizure
drugs were widely used even though most patients did not have seizures. And
while depression is common in people with brain cancer, more than 90 percent
said they never were given antidepressants. While there might have been valid reasons for the treatment choices, the
wide
variation suggests some patients are not getting appropriate care, said lead
author Dr. Susan Chang, a brain cancer specialist at the University of
California
at San Francisco. "We have a lot of work to do," she said.
The findings stem from a survey of 788 adult brain cancer patients at 52
centers
throughout the United States and Canada. The results appear in Journal of
the
American Medical Association. The survey serves as a report card on the care
of
newly diagnosed patients, and "unfortunately, the grades are sobering,"
according to a JAMA editorial. The study underscores a troubling, pervasive
problem in brain cancer: Patients get shortchanged, said Stanford University
brain tumor specialist Dr. Paul Fisher, co-author of the editorial. Many
view brain
cancer as a hopeless disease, and as a result, there is too little research
into
causes, risk factors and treatments, he said.
The study involved patients with advanced malignant gliomas, a type of
brain
cancer diagnosed in about 9,000 U.S. patients each year. Average survival
rates
range from less than a year for more advanced gliomas to about five years
for
less advanced forms. Most glioma patients are diagnosed when the tumor is
already large and root-like, infiltrating deeply into brain tissue and
making
complete surgical removal nearly impossible, Chang said. Treatment typically
involves a combination of surgery and radiation, but
high-grade gliomas generally
are considered incurable. Chemotherapy has shown
modest benefits, Chang said.
Kyla Nagel of Eugene, Ore., was diagnosed with an aggressive glioma three
years ago after a seizure. Doctors in Oregon told her there was nothing they
could do. "I went from being a healthy 23-year-old to all of a sudden you
have
cancer. I was given one year to live," said Nagel, who worried most about
her
then 1 1/2-year-old daughter. She underwent conventional treatment,
including
intravenous chemotherapy, but her cancer returned and she eventually
enrolled
in a UCSF research regimen using an experimental drug that was injected
through a catheter directly into her tumor. Nagel's outcome was not typical
—
three years later her brain scans show no signs of cancer.
Her case shows that brain cancer is not always hopeless, and it
underscores
the need for more research, Chang said. European research released last
year,
after Chang's study ended, showed improved survival rates for patients on a
newer pill, temozolomide, when used with radiation — promising results that
might change treatment practices, the JAMA study authors said.
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Arthritis
Drugs May Help Fight Cancer-Study-(Reuters-22/10/2004)
Arthritis drugs
like Celebrex and the recently withdrawn Vioxx may boost the immune
system's ability to attack brain tumors, and possibly other types of
cancer, researchers said on Friday. Doctors
at Cedars-Sinai Medical Center in Los Angeles have shown that the COX-2
enzyme is responsible for triggering a cellular process that disrupts the
body's immune response, allowing cancer cells to multiply. COX-2 blockers
-- a class that includes Pfizer Inc.'s Celebrex and Merck & Co Inc.'s
late Vioxx -- work to fight arthritis pain by blocking the
inflammation-causing COX-2 enzyme.
Results of the Cedars-Sinai study, which
appear in the Oct. 1 issue of the Journal of Immunology, support the idea
that medications attacking the enzyme may also boost the immune system's
ability to recognize and target cancer cells. "When secreted, COX-2
shuts down the immune system," said Dr. John Yu, the study's
principal investigator. "We would hope to incorporate use of COX-2
inhibitors in all patients with brain tumors."
Vioxx was withdrawn from the market last
month after twice as many patients taking it for at least 18 months
suffered heart attacks and strokes during a 2,600-patient trial of the
drug's ability to curb precancerous colon polyps. Merck also halted two
other cancer-related studies of the drug -- one in men at risk of prostate
cancer and another related to preventing colon cancer.
Using brain cancer cells, the Cedars-Sinai
researchers said laboratory tests showed that COX-2 set in motion a series
of interactions that altered messages sent to dendritic cells, which are
responsible for detecting foreign matter and instructing cancer-killing
cells to attack the tumor. But T-cells circulating in the bloodstream
showed a regulatory response against the patient's cancer cells, the study
found. "By using COX-2 inhibitors, these tumors may become more
detectable and therefore more vulnerable to destruction by the immune
system," Yu said. He said Cedars-Sinai plans to add drugs like
Celebrex to its clinical trials for brain tumors. "Studies need to be
done to see if there is relevance to other cancers," Yu added.
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Trial
Drugs Offer Hope for Brain Cancer-(HealthDayNews-20/11/2003)
By targeting specific
small proteins in cancerous brain tumors, researchers hope to develop
potent new treatments. Initial results of these experimental drugs in
mice and human cancer cells appear dramatically successful, according
to a presentation made Nov. 19 at the Molecular Targets and Cancer Therapeutics
meeting in Boston. "We have targeted ways cancer cells stimulate tumor
growth, promote their survival and create new blood vessels," says lead
researcher Dr. Jeremy Rich, an assistant professor of medicine in the
Brain Tumor Center at Duke University.
In his presentation,
Rich discussed three approaches to treatments. "One is a drug called ZD6474,
which is directed at vascular endothelial growth factor (VEGF), which
promotes blood vessel growth," Rich says. However, this drug also blocks
epidermal growth factor (EGF), which is involved in new blood vessel growth,
he adds. What is unusual about this drug is that it blocks both VEGF and
EGF, whereas most drugs block only one or the other, Rich notes. "In clinical
trials, neither single blocker has worked great," he says. "But the combination
has worked fantastically well," Rich notes. "This combination has worked
against gliomas, the most common type of brain tumor, but also other types
of tumors. . . That's a pretty exciting finding."
SB431542, another
new compound, was tested in human malignant glioma cell lines. The drug
successfully blocked the receptor protein called transforming growth factor-beta
(TGF-beta). Blocking the activity of the TGF-beta receptor also blocked
the protein PAI-1. This protein, which normally communicates with TGF-beta
in cancer cells, is a predictor of poor prognosis in patients. Another
drug combination, AEE788 and RAD001, blocked the growth of glioblastomas.
AEE788 targets epidermal growth factor receptor (EGFR) and also VEGF.
RAD001 targets mTOR. This protein is needed to regulate cell metabolism.
Without it, cells cannot grow properly. Combining these drugs blocked
tumor growth more effectively than either drug alone."These
developments will enable us to develop a cocktail approach to treating
each patient," Rich says. "We can tailor for each patient the particular
needs the patient has, based on the type of tumor."Rich
sees future treatment of brain cancers, and other cancers, as using a
combination of these drugs, customized for each patient, plus chemotherapy
and radiation. Rich believes that eventually drug therapy alone may prove
effective, eliminating the serious side effects associated with chemotherapy
and radiation. "There is really hope for the future, because treatments
are changing rapidly. There are a lot of new treatments that are showing
promise and that we hope will lessen side effects and increase our ability
to control cancers," Rich says.
Dr. Mitchel Berger,
a professor of neurosurgery and chairman of the Department Neurological
Surgery at the University of California at San Francisco, comments, "At
the UCSF Brain Tumor Research Center, we are conducting very similar trials
with similar small molecule inhibitors that do basically the same thing,
that is block EGFR, VEGF, mTOR, etc." "We are all optimistic, but must
remain cautious, since it is a long reach from animal models to humans.
Notwithstanding, many of us committed to brain tumor research and new
treatment therapies believe that we are making significant progress with
these small molecule inhibitors," he adds.
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