Chemotalk Newsletter
Chemotalk Newsletter, Vol. 26: June 1, 2010
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Omygod, July! Half a year gone. Sorry if you didn't want to be reminded...
Starting off with some excellent news, for a change:
BREAST CANCER VACCINE SHOWS PROMISE IN EARLY TRIALS
The first vaccine to prevent BREAST CANCER developed by a team of Ohio
researchers has successfully stopped tumors from growing in mice in
preliminary lab tests.
Immunologist Vincent K. Touhy and colleagues at Cleveland Clinic's
Lerner Research Institute created an agent to kill the cells that make the
proteins found in breast tumors and the mammary glands of nursing mothers.
"That was the secret, that was the strategy: Let's vaccinate against the
protein that is only expressed in lactating breasts and in breast tumors,"
said Touhy, who is also a professor of molecular medicine and pathology.
Touhy and his co-authors, whose study appears in the journal Nature
Medicine, used a single vaccination with the antigen known as ·-lactalbumin
and found it not only prevented breast cancer tumors from forming in mice
but also curbed the growth of existing tumors.
Researchers worked with a group of genetically cancer-prone mice, giving
half of them a vaccine containing·-lactalbumin and half a shot without it.
Not a single mouse vaccinated with the antigen got breast cancer, while
every mouse in the other group did. "Tumors are like drunks in a bar -- they do things they shouldn't do,"
Touhy said. "They attempt to lactate, they make these proteins. We're
trying to take the drunken element out and keep the bar safe and happy."
Touhy based his study on children's immunization programs that have
prevented illnesses like mumps and measles before their onset. He said it
is far easier to stop the development of diseases than it is to treat and
cure them once they have already appeared. He said he is hopeful that the
breast-cancer vaccine will be safe and effective in preventing the disease
in women, 1 in 8 of whom develop breast cancer at some point in their lives.
Researchers' primary concern about the new vaccine is that it might
prove to be harmful to humans, according to Touhy, but they don't anticipate
any toxicity issues based on what they saw in lab animals. "We think it could translate very closely. There's certainly a big jump
... but we never saw any damage to the mouse. We think it could be
relatively safe."
Tuohy's team is currently in need of funding in order to get approval
from the Food and Drug Administration for human trials. "I have no money to
run a clinical trial. It takes millions of dollars," Tuohy said. "We can't
do anything without that." Once he does get the necessary resources, he
predicted it will take about a year to go through the FDA regulation process
and begin testing on women.
"We're ready to go now, but we can't. We know we have a long way to go, but
we're delighted. This would be the first of its kind."
* * *
Dr. Susan Love's cautionary take on news, from her recent blog, offers some
worthwhile caveats to the vaccine story:
Friday, June 11, 2010
MOVING RESEARCH FORWARD
Every now and again a research study grabs my attention because the
investigators have gone off on a new path and have published findings that
make me think: Wow, they could be on to something! In other instances, a
study grabs me not because of what the researchers found, but because the
media made it sound so much better than it was. And sometimes it¹s a bit
both‹which is why I want to talk to you about the BREAST CANCER vaccine
that¹s been all over the news.
The idea that we can use vaccines in cancer isn¹t new. A number of
researchers have been trying to develop vaccines that could be used to treat
cancer. These vaccines are designed to try to get the body¹s immune system
to go after cancer cells, and there are a number of clinical trials now
underway testing these vaccines right now.
On the prevention front, we¹ve had more success. We now have two widely
used vaccines, one against CERVICAL CANCER, which targets the human
papillomavirus (HPV) and one against LIVER CANCER, which targets the
Hepatitis B virus (HBV).
Over the past few years, I¹ve come to believe that it is very likely
that there is a virus that is involved in the initiation of some forms of
breast cancer. So, when Nature Medicine published a letter by a research
group at the Cleveland Clinic that described the work they have done to
develop a new type of cancer vaccine that could be used to prevent breast
cancer from occurring, I was intrigued to learn more about their work.
I learned that their vaccine is not designed to target a virus. Instead,
it targets a protein that is found in women with breast cancer, but not in
healthy women (unless they are breastfeeding). They are hoping that one day
this vaccine could be given to women over 40 who were no longer
breastfeeding and at higher risk of developing cancer, so that if a tumor
started to form and release this protein, the immune system would be
prepared by the vaccine to fight it.
Is it an interesting idea? Yes. Should the media have gone nuts over it?
No‹and here¹s why. This research is in a very preliminary stage. Yes, the
research was published. But it was published as a Letter, which is more like
a notice that researchers publish to say: Look at what we just did! They are
not peer-reviewed research studies.
Also, let¹s not forget that this research is being done in mice. And
while it may sound promising to hear that none of the mice that were
vaccinated developed breast cancer, it¹s equally important to remember that
scientists stop breast cancer from developing in mice all the time.
The problem is that mice are not women, and time and time again, drugs
and vaccines that do great things in mice don¹t do anything at all to
prevent or treat breast cancer in women. So, it¹s foolish for the
researchers or their press people or the media to be acting like we have
suddenly found a way to prevent breast cancer when we don¹t even yet know if
this vaccine will be safe or effective in women!
If researchers are able to develop a safe vaccine that they think can
prevent breast cancer, it will need to be tested in tens of thousands of
women before it can be approved and then widely used. Until then, though,
we¹d all be much better off if everyone could remember that women are not
mice, and that we should save our accolades for real breakthroughs, not
media-manufactured ones.
* * *
THE STOMACH BACTERIA-RHEUMATOID ARTHRITIS CONNECTION
In early experiments with mice, scientists have found a bacteria living
in the gut may trigger an immune response that can result in RHEUMATOID
ARTHRITIS.
The gut of all mammals is populated with thousands of different types
of bacteria, many of which are essential for developing a normal immune
system. But some of these bacteria also appear to have a part in the
development of autoimmune diseases, the researchers explained.
"This is an important, rather young, area of investigation," said lead
researcher Diane Mathis, a professor of pathology at Harvard Medical School.
While these experiments in mice are still preliminary, and animal
studies often fail to produce similar results in humans, the findings could
lead to a new way of looking at autoimmune diseases and might even result in
new ways to treat or prevent them. "It may eventually be possible to
ameliorate or protect from human autoimmune diseases, arthritis and others,
by treating with probiotics, antibiotics or other inhibitors of bacterial
products," Mathis said.
The report is published in Immunity.
For the study, Mathis and colleagues raised mice genetically prone to
developing arthritis in a germ-free environment. These mice had fewer
arthritis-causing antibodies than mice raised in a normal environment.
However, when the mice were put in a non-germ-free environment and had
segmented filamentous bacteria placed in their stomachs, which is a common
gut bacteria, the animals quickly started making antibodies and developed
arthritis within four days.
"It is important to recognize that individuals do not 'catch' arthritis
via bacterial infections," Mathis said. "Rather, the bacteria trigger a
program to play out on a genetically susceptible background." In this case,
the bacteria cause the mice to make more of a type of white blood cell. The
immune system reacts to these cells as threatening antibodies that in turn
trigger rheumatoid arthritis, Mathis explained.
The research was funded by the U.S. National Institutes of Health.
The notion that bacteria in the stomach can affect the development of
autoimmune diseases such as rheumatoid arthritis is not that farfetched
since these bacteria have been linked to irritable bowel syndrome and other
such diseases. For example, stomach ulcers are caused by bacteria and
successfully treated with antibiotics.
Dr. Nancy Klimas, a professor of medicine at the University of Miami
Miller School of Medicine and a specialist in immunology, said that "this
concept of the gut flora being important to human health is considered a
rather radical concept, but it's been embraced more and more recently."
Klimas noted that a severe type of arthritis called reactive arthritis,
formerly known as Reiter's syndrome, is caused by a genetic susceptibility
and triggered by infection.
"You can cruise through your whole life with that little gene hanging
out there and never ever have a health problem, but if you get certain acute
infections those infections can trigger a huge inflammatory response and
then you are left with this lifelong arthritis condition," she said. In
the future, changing the bacteria in the gut could prevent or treat some of
these diseases, Klimas said. "This is an exciting new way of thinking, and
it could certainly change the way we practice medicine."
Klimas speculated that the overuse of antibiotics may be changing the
bacterial environment in the stomach and causing drastic increases in
diseases. "This raises the possibility that when you see illnesses that
seem to be inflammatory or autoimmune, this flora of the gut may well be
playing a role," she said.
* * *
PROSTATE CANCER VACCINE SHOWS FEW SIDE EFFECTS
The newly approved therapeutic PROSTATE CANCER vaccine, Provenge, is
safe and has few side effects, a new study finds.
"Provenge was approved based on both safety and clinical data," said
lead researcher Dr. Simon J. Hall, chair of urology at Mount Sinai Medical
Center in New York City. This safety data shows that there are very limited
side effects, Hall added.
The advantage of the vaccine for patients with metastatic
hormone-resistant prostate cancer is that it has fewer side effects than
chemotherapy, which is the only other treatment option for these patients,
Hall explained.
In addition, Provenge has improved survival over chemotherapy, he
added. The average survival time for men given Provenge is 4.5 months,
although some patients saw their lives extended by two to three years.
"This is a newly available treatment, with very limited side effects,
compared to anything else that a man would be considering in this state,"
Hall said.
Hall was to present the results at the American Urological Association
annual meeting in San Francisco.
Data from four phase 3 trials, which included 904 men randomized to
either Provenge or placebo, showed the vaccine extended survival, improved
quality of life and had only mild side effects. In fact, more than 83% of
the men who received Provenge were able to do perform activities without any
restrictions, the researchers noted.
In terms of side effects, the most common were flu-like symptoms such as
chills, fever and headache, which were seen in 3.5% of the men. Usually it
took only a day or two for the symptoms to resolve. More serious side
effects, such as infusion reactions, affected 3.5% of the patients.
Cerebrovascular problems affected 3.5% of those who received the vaccine and
2.6% of those who received placebo, Hall's group found.
Dr. Nelson Neal Stone, a clinical professor of urology and radiation
oncology at Mount Sinai School of Medicine in New York City, said that "the
side effects are like having the flu and they can be managed with aspirin."
However, Stone pointed to one big drawback to Provenge: cost. "I've heard
$30,000, I've heard $90,000 ... I have no idea what it's going to cost. And
who's going to pay for it?" he said.
Provenge is a therapeutic (not preventive) vaccine that is made from the
patient's own white blood cells. Once removed from the patient, the cells
are treated with the drug and placed back into the patient. These treated
cells then cause an immune response, which in turn kills cancer cells, while
leaving normal cells unharmed.
According to the FDA, Provenge is given intravenously in a three-dose
schedule delivered in two-week intervals. The vaccine was developed by
Seattle-based Dendreon Corp., which conducted initial studies among men with
advanced prostate cancer who had already failed standard hormone treatment.
According to American Cancer Society estimates, more than 192,000 new
cases of prostate cancer are diagnosed in the United States each year, and
27,360 men die from the disease. Prostate cancer is the most common form
of cancer diagnosed in American men, after skin cancer.
More than 2 million American men who have had prostate cancer at some
point are still alive today. The death rate is going down and the disease is
being found earlier, according to the cancer society.
* * *
Another prostate cancer study caught my attention because it struck a
personal note. My father's brother was diagnosed with prostate cancer when
he was in his 50s. He did die of prostate cancer -- at the age of 96. He
was monitored for over 40 years, but not treated until the disease showed
signs of activity. He lived a long, healthy life.
VALUE OF MONITORING LOW-RISK PROSTATE CANCER ASSESSED
New research is offering more insight into the value of closely
monitoring patients who appear to have low-risk forms of PROSTATE CANCER
instead of immediately treating them.
There's been a debate in recent years over whether doctors are treating
prostate cancer when they don't need to. In some cases, doctors use
"watchful waiting" to monitor patients to see if signs of prostate cancer
worsen.
In one preliminary study, researchers in Canada studied 453 men with
lower-risk prostate cancer and determined how many would have been offered
treatment instead of monitoring based on such commonly used "triggers" as
measurements of prostate-specific antigen (PSA). The rates ranged from 42%
to 84%.
In another study, researchers from San Francisco analyzed the safety and
value of monitoring in a group of 477 men, most of whom had been diagnosed
with low-risk disease at about 62 years of age. The findings are scheduled
to be presented at the American Urological Association annual meeting in San
Francisco.
"Overdetection should not be used synonymously with overtreatment when
it comes to prostate cancer," Dr. J. Brantley Thrasher, of the University of
Kansas Medical Center, who will moderate the discussion of the findings,
said in a news release from the association. "These two studies alone show
just how valuable active surveillance protocols can be when disease is
managed well, and treatment is recommended appropriately."
* * *
MAKING YOUR WAY THROUGH THE FOG OF CHEMOTHERAPY
For many people with cancer, CHEMOTHERAPY can be a lifeline to the
future. And more aggressive, high-dose therapy has been shown to produce
better results. But there's a downside: Chemotherapy is linked to a mental
fog called "chemo brain."
For years, people's complaints were dismissed as "all in your head,"
but that's no longer the case. It's now the topic of serious research, with
investigators working hard to figure out why it happens and what can be done
to help those who suffer from it.
Yet even with the added focus on chemo brain research, many doctors who
care for cancer patients are either unaware of the phenomenon or don't think
to discuss the possibility with their patients, said Saskia Subramanian, a
research sociologist at the David Geffen School of Medicine at the
University of California, Los Angeles, who has researched and published on
chemo brain and wrote After the Cure: The Untold Stories of Breast Cancer
Survivors. She encourages patients to bring it up themselves, especially if
they think they're experiencing it.
Among the symptoms:
* Forgetting things that are usually easy to recall, such as names or words
* Having problems concentrating
* Having difficulty multi-tasking
* Being slower at doing routine tasks
Exactly how many people develop chemo brain is unknown, agreed
Subramanian and Christina Meyers, professor and chief of neuropsychology at
the M.D. Anderson Cancer Center in Houston, who has researched the condition
for more than two decades. "I would say more than half of the cancer
patients in active treatment have some kind of symptomology" related to
chemotherapy, Meyers said. "It could range from pretty mild to so severe
that a person is unable to perform their normal activities."
Subramanian said the estimates vary widely, from 20 or 30 percent to 90
percent of chemo patients. "My guess is it's somewhere in the middle," she
said. "My suspicion is it has to do with how aggressive the treatment is."
Because the trend is toward more aggressive chemo, the pressure is on to
learn more about the condition, what's behind it and how people can cope.
Researchers who've done studies involving imaging of the brain have
found changes in the brain activity of breast cancer patients treated with
chemotherapy, compared with those who didn't get chemo.
Meyers said that recent studies have also found acute injury to brain
cells and damage to myelin, the white matter that coats nerve cells.
They are important clues, but much is still unknown about chemo brain.
Even so, no one is suggesting that people opt out of chemo that is
recommended to them, Subramanian noted. "It's not a reason to forego needed
chemo," she said.
Some researchers are looking at medicines in use for such conditions as
depression, attention-deficit/hyperactivity disorder and dementia to see if
the drugs might help those with chemo brain. And research is also underway
to develop animal models and come up with new drugs to counteract the
effects of chemo brain, Meyers said.
But until then, she said, anyone having chemotherapy would be wise to
develop compensatory measures. These could include:
* Setting up a "memory station" at home -- one place to keep keys, important
papers and work-related items you need to take to the office.
* Using a day planner or personal digital assistant for reminders about
meetings and appointments.
* Using checklists. One might be a list of things to do when leaving work:
Log off your network, turn off your computer, turn on voice mail, turn off
the coffee pot, turn off the lights -- anything that needs to get done.
* Parking in the same place at work, at the mall, wherever you go often.
* Not trying to multi-task. Even if you were champion before, Meyers said,
for now do just one task at a time.
Certain strategies, though, are not helpful, Meyers added. For
instance, one thing that she said doesn't work is doing repetitive mental
exercises, such as crossword puzzles or video games. She said many people
with chemo brain tell her they try that, but she said it doesn't seem to
translate to remembering names better.
Also, the experts agreed that anyone complaining of chemo brain ought
to be evaluated to make sure that other problems -- such as depression or a
thyroid problem -- aren't contributing to the fog and mental slowdown.
* * *
The American Society of Clinical Oncology (ASCO) held their annual
contention in Chicago in June. Here are some of the promising
presentations:
AMG 479 PRODUCES PROMISING RESULTS IN METASTATIC PANCREATIC CANCER
According to the results of a Phase II clinical trial, treatment of
metastatic PANCREATIC CANCER with a combination of AMG 479 and Gemzar®
(gemcitabine) resulted in better progression-free and overall survival than
treatment with Gemzar alone.
Pancreatic cancer is one of the deadliest forms of cancer. Each year,
approximately 43,000 people are diagnosed with pancreatic cancer in the
United States and more than 37,000 die from the disease. It is often
diagnosed at an advanced stage, and improved approaches to early detection
and treatment are important research priorities.
AMG 479 is an investigational therapy that targets the type 1
insulin-like growth factor receptor (IGF-1R). Signaling through this
receptor plays an important role in the regulation of cell growth and
survival.
To evaluate the potential role of AMG 479 in the treatment of pancreatic
cancer, researchers conducted a Phase II clinical trial. The study involved
121 patients with metastatic pancreatic cancer. Patients were assigned to
one of three treatment groups: 1) Gemzar alone; 2) Gemzar plus AMG 479; or
3) Gemzar plus conatumumab. Conatumumab is another investigational targeted
therapy.
* At six months, overall survival was 57% among patients treated with Gemzar
plus AMG 479, 59% among patients treated with Gemzar plus conatumumab, and
50% among patients treated with Gemzar alone.
* At 12 months, overall survival was 39% among patients treated with Gemzar
plus AMG 479, 20% among patients treated with Gemzar plus conatumumab, and
23% among patients treated with Gemzar alone.
* Progression-free survival was 5.1 months among patients treated with
Gemzar plus AMG 479, 4.0 months among patients treated with Gemzar plus
conatumumab, and 2.1 months among patients treated with Gemzar alone.
Serious (grade 3 or higher) side effects that were more common among
patients treated with Gemzar and AMG 479 than among patients treated with
Gemzar alone included neutropenia (low white blood cell counts),
thrombocytopenia (low platelet counts), and fatigue.
These results suggest that the addition of AMG 479 to Gemzar may improve
survival with metastatic pancreatic cancer. AMG 479 will be further
evaluated in a Phase III clinical trial.
* * *
...and this:
COMBINATION CHEMOTHERAPY IMPROVES SURVIVAL IN ELDERLY LUNG CANCER PATIENTS
Among patients age 70 or older with advanced NON-SMALL CELL LUNG CANCER
(NSCLC), treatment with a combination of two chemotherapy drugs‹paclitaxel
and carboplatin‹results in better progression-free and overall survival than
treatment with single-agent chemotherapy.
Nonsmall cell lung cancer (NSCLC) accounts for approximately 85% of all
lung cancers.
At least 30% of NSCLC cases occur in people age 70 or older, but there
is limited information about how best to treat older patients. As a result
of the limited information and concern that elderly patients will not be
able to tolerate aggressive treatment, older patients may be treated with
single-agent chemotherapy rather than combination chemotherapy.
To explore treatment options for older patients with advanced NSCLC,
researchers in France conducted a Phase III clinical trial in 451 patients
between the ages of 70 and 89. Patients were assigned to receive either
combination chemotherapy with paclitaxel and carboplatin, or single-agent
chemotherapy with gemcitabine or vinorelbine.
* Overall survival was 10.4 months among patients treated with combination
chemotherapy and 6.2 months among patients treated with single-agent
chemotherapy.
* Survival without cancer progression was 6.3 months among patients treated
with combination chemotherapy and 3.2 months among patients treated with
single-agent chemotherapy.
* Combination chemotherapy had acceptable toxicity, but did increase the
likelihood of moderate to severe neutropenia (low white blood cell counts).
These results suggest that older patients with advanced NSCLC can be
considered for the same aggressive therapy as younger patients.
* * *
Also from the ASCO meeting:
IPILIMUMAB IMPROVES OUTCOMES IN ADVANCED MELANOMA
Among patients with previously treated, advanced MELANOMA, treatment
with the investigational drug ipilimumab improved overall and
progression-free survival.
Each year in the United States, there are roughly 68,000 new diagnoses
of melanoma and 8,700 deaths from the disease. Finding effective treatments
for advanced melanoma has been challenging.
Ipilimumab is an investigational drug that targets a molecule known as
CTLA4, which is found on the surface of T cells and is thought to inhibit
immune responses. By targeting this molecule, ipilimumab may enhance the
immune system¹s response against tumor cells.
To evaluate ipilimumab in the treatment of melanoma, researchers
conducted an international Phase III clinical trial among 676 patients with
previously treated, Stage III or Stage IV melanoma. Patients were assigned
to one of three treatment groups: 1) ipilimumab; 2) ipilimumab plus the
gp100 vaccine; or 3) the gp100 vaccine alone.
The gp100 vaccine is an experimental melanoma vaccine that is also
designed to stimulate T cells to attack melanoma cells. In previous studies
it has shown modest anticancer activity and was superior to treatment with
IL-2.
* Median overall survival was 10 months in the groups that received
ipilimumab, compared with 6.5 months in the group that received the gp100
vaccine alone.
* Two-year survival was 24% among patients who received ipilimumab alone,
22% among those who received ipilimumab and the gp100 vaccine, and 14% among
those who received the gp100 vaccine alone.
* Six-month progression-free survival was 30% among patients in the
ipilimumab groups and 11% among patients in the group that received the
gp100 vaccine alone.
* Ipilimumab was generally well tolerated, but 10-14% of patients treated
with ipilimumab experienced sometimes severe side effects such as rash and
colitis (inflammation of the colon). The frequency among patients treated
with gp100 was roughly 3%.
These results suggest that ipilimumab may delay cancer progression and
improve overall survival among patients with previously treated, advanced
melanoma. The addition of the gp100 vaccine to ipilimumab did not appear to
further improve outcomes.
* * *
The following piece, including the study of Ipilimumab, appeared in a recent
New York Times piece, that puts some of these advances into clearer
perspective:
SCIENTISTS CITE ADVANCES ON TWO KINDS OF CANCER
Opposite Strategies Offer New Hope, Not A Cure
By Andrew Pollack
Using two opposite strategies, one focused and one broad, scientists say
they have made progress in taming two of the most intractable types of
cancer.
The focused approach shrank tumors significantly in a majority of
patients with advanced LUNG CANCER marked by a specific genetic abnormality.
Even though the clinical trial was small (just 82 people, with no
control group), the results were considered so striking for such sick
patients that the study was featured at the main session of the annual
meeting of the American Society of Clinical Oncology.
"This is a phenomenal example of finding the right patient and the right
drug early on," said Dr. Pasi A. Janne of the Dana-Farber Cancer Institute
in Boston, who was involved in the trial.
The broader strategy uses a drug that could potentially become a
universal treatment for all types of cancer. It works by releasing a brake
on the body's immune system, letting the immune system attack the cancer
more vigorously.
In a study of patients who had advanced MELANOMA, those who got an
experimental drug lived a median of about 10 months, compared with 6.4
months for those in a control group. After two years, about 23% of those
who got the drug were alive, compared with 14% in the control group.
Lung cancer and melanoma are among the hardest cancers to treat. So the
studies are being viewed as significant advances, though far from cures.
Dr. Steven J. O'Day of the Angeles Clinic and Research Institute in
Santa Monica, California, a lead investigator in the melanoma trial, called
the results "historic", and added "This is the first randomized
placebo-controlled trial ever to show a survival benefit in Stage 4
melanoma."
Bristol-Myers Squibb, which sponsored the trial, is planning to apply
for regulatory approval to sell the drug, ipilimumab.
The lung cancer drug, by contrast, blocks an aberrant protein called ALK
that is found in only about 5% of non-small-cell lung tumors. But in
patients whose tumors have this aberration, the drug seems to work wonders.
The tumors shrank significantly in 57% of the 82 patients, and they remained
stable in 30% more.
Beverly Sotir, 71, of Belmont, Mass., who has been taking the pills as
part of the trial since July, said her tumors had shrunk without
debilitating side effects. "For someone who's been on chemo before, this is
like a miracle drug," she said. "You feel yourself. You look yourself."
Pfizer, which sponsored the study, has started a more definitive trial
aimed at winning approval of the drug, crizotinib.
There are caveats. The effects of crizotinib can wear off, though 71%
of the patients in the trial were free of cancer progression for six months.
As for the melanoma drug, because it removes checks on the immune
system, 10% to 15% of patients who took it in the study suffered severe side
effects because their immune systems attacked their own organs. Seven
patients out of 540 who got ipilimumab died from these immune effects,
according to a report of the study published by the New England Journal of
Medicine.
Efforts to harness the immune system to fight cancer have suffered
setback after setback. Because tumor cells are mutate forms of the body's
own cells, not an invading pathogen, they do not usually elicit a strong
immune response.
But the Food and Drug Administration this year approved a "cancer
vaccine" for prostate cancer called Provenge, so-called because it trains
the immune system to attack the patient's tumors. Most such vaccines focus
on a single type of cancer, or are even tailored to individual patients.
Ipilimumab, by contrast, is a more general immune booster. It blocks a
protein called CTLA-4 that acts as a brake on T cells, the soldiers of the
immune system. It is already also being tested against LUNG and PROSTATE
CANCER.
Still, if a tumor does not elicit a strong immune response to begin
with, then just keeping the response going longer would not help much, just
as lifting ones foot from the brake usually will not make a car go faster if
the accelerator is not pressed.
In at least one other melanoma trial, conventional chemotherapy drugs
achieved median survival of about 10 months, the same as ipilimumab.
`Dr. Charles M. Balch, a melanoma expert at Johns Hopkins who was not
involved in the trial, called the results "a single, not a home run," though
he added that for this disease even a single was important.
About 68,000 Americans are expected to get melanoma this year, with
8,700 deaths, according to the American Cancer Society. The numbers have
been increasing, probably because of sun exposure decades ago.
The trial involved 676 patients in the United States and 12 other
countries with previously treated metastatic melanoma. They received either
ipilimumab or an experimental cancer vaccine of both. Those who got
ipilimumab alone did as well as those who got both, suggesting the vaccine
had little effect.
Dr. Petra Rietschel of the Montefiore-Einstein Center for Cancer Care in
the Bronx said melanoma experts were equally or even more excited about a
drug being developed by Plexxikon and Roche that blocks a particular protein
called B-FAR that is aberrant in more than half of all cases of the disease.
That is similar to the approach of crizotinib, Pfizer's lung cancer drug.
They are part of a trend to genetically analyze a patient's tumor and find
drugs that block the particular genetic anomaly that drive that tumor's
growth.
Pfizer developed crizotinib to block another protein called MET. The
fact that the drug also blocked ALK was considered unimportant.
But in 2007, after the clinical trial had started, Dr. Hiroyuki Mano and
colleagues at Jichi Medical University in Japan reported that in a small
number of lung cancers, there was a chromosome translocation that brought
the gene for ALK together with the gene for another protein called EML4.
That created a fusion protein that spurred tumor growth. Dr. Mano had
discovered this by systematically testing all the active genes in a tumor
removed from a lung cancer patient.
Pfizer turned on a dime and began enrolling lung cancer patients with
this fusion protein in the trial. Japanese patients began flying to South
Korea, the nearest place with trial sites.
Dr. Mano said the first Japanese patient who went was so sick -- heavily
dependent on oxygen tanks and unable to swallow -- that he had to be taken
to the airport by medical helicopter and met by an ambulance at the airport
in Seoul. Two weeks later, Dr. Mano said, he went to Seoul to check on the
patient. The man no longer needed oxygen and was walking in the
neighborhood each day looking for good restaurants. The patient returned to
Japan and lived for several more months.
Scientists said the ALK gene aberration tends to be more frequent in
younger patients and nonsmokers. Experts say that even though the drug
might be useful for only 5% of non-small-cell lung cancer patients, that
would still be about 10,000 people a year in the United States and 40,000
worldwide.
Finding drugs for each subset of tumors will take years. And cancers
can mutate and become resistant to drugs blocking particular abnormalities.
Dr. James Allison, who paved the way for ipilimumab with work he did at
the University of California, Berkeley, said the immune therapies might be
helped by such mutations. So the targeted drugs and the immune boosting
ones might work best together.
"It's the ultimate personalized treatment for cancer," said Dr. Allison,
who is now chairman of immunology at the Memorial Sloan-Kettering Cancer
Center.
* * *
NEW CLUES TO PREVENTING MEMORY LOSS FROM MS
A new study suggests that being mentally active may help reduce memory
and learning problems that often occur in people with MULTIPLE SCLEROSIS.
The study included 44 people, about age 45, who'd had MS for an average
of 11 years. Even if they had higher levels of brain damage, those with a
mentally active lifestyle had better scores on tests of learning and memory
than those with less intellectually enriching lifestyles.
"Many people with MS struggle with learning and memory problems," study
author James Sumowski, of the Kessler Foundation Research Center in West
Orange, N.J., said in an American Academy of Neurology news release. "This
study shows that a mentally active lifestyle might reduce the harmful
effects of brain damage on learning and memory."
"Learning and memory ability remained quite good in people with
enriching lifestyles, even if they had a lot of brain damage [brain atrophy
as shown on brain scans]," Sumowski continued. "In contrast, persons with
lesser mentally active lifestyles were more likely to suffer learning and
memory problems, even at milder levels of brain damage."
Sumowski said the "findings suggest that enriching activities may build
a person's 'cognitive reserve,' which can be thought of as a buffer against
disease-related memory impairment. Differences in cognitive reserve among
persons with MS may explain why some persons suffer memory problems early in
the disease, while others do not develop memory problems until much later,
if at all."
Peter Arnett of Penn State University added that "more research is
needed before any firm recommendations can be made," but that it seemed
reasonable to encourage people with MS to get involved with mentally
challenging activities that might improve their cognitive reserve.
* * *
And finally ...
SPRYCEL MAY BE MORE EFFECTIVE THAN GLEEVEC FOR INITIAL TREATMENT OF CML
In the initial treatment of CHRONIC MYELOID LEUKEMIA (CML), Sprycel®
(dasatinib) produces higher response rates than Gleevec® (imatinib).
Most cases of CML are characterized by a chromosomal abnormality‹the
Philadelphia chromosome‹in which genetic material is exchanged between
chromosome 9 and chromosome 22. This exchange brings together two genes: BCR
and ABL. The combination of these two genes into the single BCR-ABL gene
results in the production of a protein that contributes to uncontrolled cell
growth.
Recognition of the pivotal role of the BCR-ABL protein in CML led to the
development of Gleevec, which blocks the activity of this protein. Gleevec
produces high rates of remission among patients with chronic-phase CML,
often with few side effects, and has dramatically changed the treatment of
this disease.
Sprycel also targets the BRC-ABL protein, and has provided an important
option for patients who are resistant or intolerant to Gleevec. Sprycel has
not yet been approved for the initial treatment of CML.
To compare Gleevec and Sprycel for the initial treatment of CML,
researchers conducted a study among 519 patients with newly diagnosed,
Philadelphia chromosome-positive, chronic-phase CML. Patients were assigned
to receive either Gleevec or Sprycel. One of the main outcomes of interest
was the complete cytogenetic response rate. A complete cytogenetic response
is the complete disappearance of cells with the Philadelphia chromosome.
* After one year, the complete cytogenetic response rate was 77% among
patients treated with Sprycel and 66% among patients treated with Gleevec.
* Rates of major molecular response (another marker of drug effectiveness)
were 46% among patients treated with Sprycel and 28% among patients treated
with Gleevec.
* Both drugs were generally well tolerated.
These results suggest that Sprycel may be more effective than Gleevec
for the initial treatment of CML. Researchers will continue to follow the
study participants in order to determine whether there are differences in
progression-free and overall survival between study groups.
* * *
This story comes from Market Watch, where companies often announce news they
believe will positively affect their stock:
NOVARTIS MULTIPLE SCLEROSIS DRUG WINS ADVISORY NOD
Novartis said a key committee has backed the approval of the first oral
drug to treat REMITTING MULTIPLE SCLEROSIS, giving a boost to the Swiss
drugmaker's shares, even as questions surround the side effects of taking
it.
Novartis said an advisory committee to the U.S. Food and Drug
Administration has recommended approval of FTY720 for patients with
relapsing multiple sclerosis, the most common form of the disease. While
the FDA doesn't have to accept the advisory committee's view, it's usually
a strong indicator of approval.
The Basel, Switzerland drugmaker said the recommendation came on data
showing FTY720, or Gilenia as the company is planning to call it, worked
better than one of the most commonly prescribed treatments, Biogen's Avonex.
Many questions are remain unanswered. "As expected, the efficacy of the
drug is undisputed and strong," said Andrew Weiss, an analyst at Vontobel.
"However, the adverse events associated with the intake of the drug are an
issue."
The drug is linked to side effects including macular edema, decreased
lung function and cardiovascular toxicity. That's led the panel to suggest
that after approval, a trial be conducted to evaluate a previously untested
lower dosage.
Oliver Kaemmerer, an analyst at WestLB, said the drug may generate peak
annual sales of at least $1.5 billion, and could reach up to $3.9 billion if
the drug's label doesn't carry restrictions and there are no further safety
findings.
The drug, which the analyst estimates will cost around $30,000 per year
and may be launched in the fourth quarter of this year.
* * *
Very often, there isn't a plethora of good news about rheumatoid arthritis
treatment. So when a new story appears, even if it turns out to be a dead
end research-wise, it deserves a hearing.
RHEUMATOID ARTHRITIS HALTED BY NEW "SUICIDE" MOLECULE
When you hear the terms "suicide molecule," "stealth," "going
rogue," and "Casper the ghost," you might think they refer to some kind of
modern warfare tactic. You're not that far off. Modern medicine is coming
up with some pretty covert and creative ways to wage war on disease.
Recently, a researcher from Northwestern University's Feinberg School of
Medicine has cooked up a clever way to stop and even reverse RHEUMATOID
ARTHRITIS. He's created a molecule that masquerades as a "suicide
molecule." It can penetrate overactive immune cells, causing them to
self-destruct.
Rheumatoid arthritis affects approximately 1.5 million adults and
involves immune cells that refuse to die after attacking an invading virus
or bacteria. These cells, called macrophages, then "go rogue," moving
throughout the blood, joints, cartilage, and bone where they build up. So
far, no non-toxic and effective way to prevent this phenomenon has been
found.
Harris Perlman, associate professor of medicine at Feinberg thinks his
new molecule, which he calls "Casper the Ghost," could be the solution
doctors have been looking for. He discovered that the overactive immune
cells that cause rheumatoid arthritis are deficient in a molecule called
Bim, which would normally give them the signal to self-destruct. Perlman
created his "ghost" molecule as an imitation of a Bim, designed to correct
this shortage. In tests on mice, the treatment worked 75% of the time, and
it did so without the dangerous side effects of current treatments.
Perlman is hopeful about the future of his technique. "The best part was
we didn't see any toxicity. This has a lot of potential for creating an
entirely new treatment for rheumatoid arthritis." Doctors currently treat
the disease with low-level CHEMOTHERAPY and steroids, which are frequently
accompanied by severe side effects. Other recent treatments have proven
inconsistent and also cause side effects.
* * *
By now, you know my feeling about nurses. So it's a special treat for me to
end this newsletter with a recent editorial from The New York Times, written
by an oncology nurse:
IS THERE A NURSE IN THE HOUSE?
By Theresa Brown
Pick any of the hospital dramas that have run for decades on American
TV, and chances are the heroes are the doctors, running to a patient's
bedside to save a life whenever an alarm goes off.
Doctors can indeed be heroes. But when a patient takes a sudden turn
for the worse, it's the nurses who are usually the first to respond. Each
patient has a specific nurse assigned to watch over him, and it is that
nurse's responsibility to react immediately in the event of an emergency.
That's getting harder to do, though. Cost-cutting at hospitals often
means fewer nurses, so the number of patients each nurse must care for
increases, leading to countless unnecessary deaths. Unless Congress
mandates a federal standard for nurse-patient ratios, those deaths will
continue.
A few states already have minimum ratio requirements, most notably
California, which in 2004 instituted a one-to-five ratio for surgery
patients -- as well as a one-to-four ratio in pediatrics and a one-to-two
ratio in intensive care -- after a decade-long fight led by the California
Nurses Association.
Laws like these could make a huge difference nationally. A recent study
led by Linda Aiken, a professor at the University of Pennsylvania School of
Nursing, found that New Jersey hospitals would have 14% fewer surgical
deaths if they matched California's ratio, while Pennsylvania would have 11%
fewer. Professor Aiken looked at surgical units only, but it's reasonable
to assume that the percentages would apply on any hospital floor.
The reason is simple. The fewer patients each nurse oversees, the
easier it is to respond when a patient has an emergency, like a sudden,
severe decline in oxygen saturation, a precipitous drop or rise in blood
pressure or a heart rate that suddenly skyrockets. A nurse juggling the
needs of too many patients might not have the time to notice, let alone
respond.
Nevertheless, hospitals have resisted mandated ratios. While higher
personnel costs are most likely at the core of their opposition, they also
argue that hospitals that already have good ratios will use the standards to
justify cutting the number of nurses on each floor.
This is a reasonable concern, but one that rarely if ever proves true.
In more than a decade of research, Professor Aiken reports never seeing such
reductions in the wake of mandated ratios. Moreover, if hospitals were so
callous, why do so many -- including my own 00 often meet or exceed
California's standards?
Moreover, it's not as if such low ratios are a luxury; there's a reason
why minimum ratios are also called "safe staffing levels." Say a nurse
can't come in because of a family emergency. Then another nurse becomes ill
and has to go home. The charge nurse will call around to other staff
members, trying to find last-minute replacements. But sometimes there's no
one to come in and no nurses available at the last minute to "float" to the
understaffed unit. The lower the ratio, the more likely the nursing staff
will be able to cover if and when personnel suddenly became unavailable.
The real issue, of curse, is cost. There's no denying that hiring more
nurses is more expensive in the short term. But having too few nurses leads
to burnout, not only because it's too much work, but because good nurses
quit from the stress of knowing they can't keep their patients safe.
Mandated ratios could ultimately save money, because they would reduce both
staff turnover and the number of patients who became critically ill due to
insufficient care.
And it's true that, as some argue, the nurse-patient ratio is not the
only factor in improving the quality of care. But the data provided by
Professor Aiken and others clearly shows that hospitals with the best
staffing ratios have the best outcomes overall.
The benefits of mandating nurse-to-patient ratios are so compelling that
last year Senator Barbara Boxer, Democrat of California, introduced a bill
to set national standards, while Representative Jan Schakowsky, Democrat of
Illinois offered similar legislation in the House. Yet both bills have
languished in committee.
On television the doctors and nurses always arrive in time to help a
struggling patient. In real life, when nurses are overworked, a patient in
distress may be overlooked.
To be the nurse in such situations feels horrible. But for the patient
it can be far worse.
* * *
If you haven't checked out my website yet, as a medical professional friend
suggested, I should put it at the end of the Newsletter. (One would think I
would know this, I'm a marketing person, but...no.) The site is www.elainejesmer.com
See you next month.
* * *
And if you have any thoughts of how this newsletter could be
improved, please email me directly, at jesmer_e@pacbell.net
Elaine Jesmer
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