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:


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


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.

* * *


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.

* * *


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.


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."

* * *


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:


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:


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:


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.

* * *


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 ...


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.

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This story comes from Market Watch, where companies often announce news they believe will positively affect their stock:


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.

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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.


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.

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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:


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.

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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,  The site is

See you next month.

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And if you have any thoughts of how this newsletter could be improved, please email me directly, at

Elaine Jesmer

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