Chemotalk Newsletter

Chemotalk Newsletter, Vol. 19:  November 1, 2009

back to newsletter archive

Hello, Everyone, once again ... And Happy Thanksgiving, in advance.


A new way to classify STOMACH CANCERS could lead to more effective treatments and improved long-term survival for people with the disease, researchers say.

For a study published online Oct. 1 in PLoS Genetics, the researchers analyzed 301 stomach tumors from people in Australia, Singapore and Great Britain, classifying the cancers according to the signaling pathways the tumors use to grow and spread. Currently, stomach cancers are classified by cell type or structure.

"We identified three oncogenic pathways that were activated in over 70% of the gastric tumors we examined," lead author Chia Huey Ooi, a research fellow at the Duke-National University of Singapore Graduate Medical School, said in a Duke news release. "We also found that combinations of these pathways are significantly related to patient survival."

Less than a quarter of stomach cancer patients live longer than five years after surgery. The disease is resistant to chemotherapy, and new biologic-based treatments have not proven very effective. Using this new system, doctors could classify patients according to the pathway profile of their tumor and design treatments to interrupt the signals used by the pathways.

"These findings may give us the first way to truly offer our gastric cancer patients personalized medicine," said the study's senior author, Dr. Patrick Tan, also from the Duke-NUS medical school and the Genome Institute of Singapore.

* * *


An experimental treatment for ADVANCED MELANOMA promotes rapid shrinking of tumors, according to a new study.

The phase I extension trial includes patients with the cancer-causing mutation of the BRAF gene, which is associated with about 50% of melanomas and 5% of colorectal cancers.

The patients were given 960 milligrams of PLX4032 twice a day. Of the 22 patients evaluated to date, 14 (64 percent) showed at least 30% shrinkage in the diameter of tumors for at least a month -- the official criteria for partial response to the treatment. Another six of the 22 patients also showed a response, but it was too early to determine whether the tumors would shrink enough to meet the criteria for partial response.

The findings were presented in Berlin at a meeting of the European Cancer Organization and the European Society for Medical Oncology.

"We are very excited about these results. Of the 22 patients we have been able to evaluate so far, 20 have had some objective tumor shrinkage. This is impressive as they all had metastatic disease, and most of them had failed several prior therapies," said trial co-leader Dr. Paul Chapman, an attending physician on the melanoma/sarcoma service at Memorial Sloan-Kettering Cancer Center in New York City.

"A lot of these patients were pretty sick, but many of them had a significant and rapid improvement in the way they function. We've had patients come off oxygen, and we've got several patients who have been able to come off narcotic pain medication soon after starting treatment," Chapman said.

"What makes this treatment different from standard chemotherapy is that standard chemotherapy attacks the machinery involved in cell division; so to stop the cancer cells dividing uncontrollably, most standard chemotherapy aims to block the mechanism of division by interfering directly with DNA replication or with microtubules in the dividing cells," he explained.

"PLX4032 is different because it attacks the genetic program that is causing the cells to divide uncontrollably, and we think the BRAF mutation is driving that program. The drug is blocking the genetics of the tumor, rather than trying to interfere with the proliferation of the cells and, as a result, there are fewer side effects, although there are some. We are seeing some pretty dramatic and rapid responses, and they are occurring in sites where we rarely see responses to chemotherapy, such as in the bone."

Chapman noted that "we don't know yet how long these responses will last, and we have had patients whose cancer has progressed after initially responding; so we are putting a lot of effort into studying the patients who do relapse, trying to understand how their tumors have become resistant.

"In addition, one of the main side effects we've seen is that some patients develop early, non-melanoma skin cancers, such as squamous cell skin cancer. We are very vigilant about this, and although they are very easy to cut out, it's something we are keeping a close eye on."

A phase II trial involving 90 patients will start at the end of this year, and a phase III trial involving several hundred patients is scheduled to begin at the end of this year or early next year.

In related news from the cancer meeting in Berlin, researchers said they've shown that ultrasound can be used to identify whether cancer has started to spread in melanoma patients, and to what extent. This information can help doctors decide how much surgery, if any, a patient requires and predict the patient's likelihood of survival.

"We have identified two ultrasound patterns of lymph node metastasis in melanoma patients which can identify correctly any amount of tumor cells in the sentinel lymph nodes in 75 to 90% of cases before proceeding to surgery on the sentinel lymph nodes," said Dr. Christiane Voit, head of the diagnostic unit at the Skin Cancer Center at the Medical University of Berlin. Since 2001, she and her colleagues have tested the use of ultrasound in diagnosis and treatment planning of 850 melanoma patients. The research findings need to be confirmed in multi-center, randomized trials, Voit said.

* * *


MediGene AG (Frankfurt) received feedback from the UK MHRA (Medicines and Healthcare products Regulatory Agency) regarding the in-vitro studies conducted with the drug candidate RhuDex(TM) for the treatment of RHEUMATOID ARTHRITIS. These in-vitro studies examined potential effects of RhuDex(TM) on the vascular system or any arteriosclerotic blood vessels. Since these tests did not suggest any negative effects of RhuDex(TM), the MHRA agreed to a continuation of the drug candidate's clinical development, without requesting any further in vitro or ex vivo data.

MediGene is planning to resume the Phase I clinical development for RhuDex, thus laying the necessary foundation for a clinical Phase II trial in patients. As the extended plan for clinical development is drafted, MediGene will coordinate with the competent regulatory authorities.

Following a successful Phase IIa trial in 29 patients during the first six months of 2008, MediGene conducted a clinical Phase I trial of a new tablet formulation of RhuDex. This trial was put on hold in July 2008, following the death of a trial participant from myocardial infarction. The autopsy revealed severe impairment of cardiac function of the volunteer deemed to be present prior to admission to the trial, as well as other scientific findings. MediGene considered any causal correlation between the death of the patient and the administration of RhuDex to be unlikely, but for safety reasons the Company proceeded to test RhuDex in a series of further laboratory studies in coordination with the MHRA.

Said Dr. Axel Mescheder, CSO & CDO of MediGene AG: "We are very happy that we are in a position to continue clinical development of this innovative drug candidate for the treatment of immune-mediated diseases. We are pleased that the decision by MHRA is in line with MediGene's assessment."

RhuDex is being developed as a disease-modifying drug for the treatment of rheumatoid arthritis, aiming at the successful group of Disease-Modifiying Antirheumatic Drugs (DMARDs). As the first orally administered and at the same time specifically effective DMARD, RhuDex is targeted at stopping T-cell activation by specifically blocking the very well-defined target protein CD80, thus inhibiting the release of cytokines which stimulate inflammation. Thus the disease-causing mechanism inhibited in a very specific way.

More than 1% of the world population is affected by this chronic, systemic disease of the connective tissue which leads to pain, deformity, restricted mobility, and often to stiffening of the joints affected.

* * *


A pocket-size device under development could soon help monitor how well estrogen-positive breast cancer treatments are working and help assess breast cancer risk by measuring levels of estrogen.

"We've developed a 'lab on a chip,' which is useful for making quantitative measurements of estrogen in samples of blood or tissue," said Aaron Wheeler, the Canada research chair of bioanalytical chemistry at the University of Toronto and a co-author of a report on the device in an issue of Science Translational Medicine.

The new device relies on a method called digital microfluidics. The technique is being used to analyze hormones found in tiny samples of blood, and breast cancer tissue.

Instead of moving electrons across tiny wires, it electronically manipulates minute droplets of fluid on the surface of a microchip, integrating many different lab functions so fewer are needed. Hormones are extracted, purified and analyzed. And it's all done on a device that can fit on the palm of the hand.

The "lab on a chip" technique, already under study in other areas, takes raw, unprocessed tissue and delivers results rapidly. Estrogen can be measured in minutes.

It also requires much tinier samples than those needed by conventional methods, said Dr. Noha Mousa, also a co-author of the report, who is working on her Ph.D. in medicine at the University of Toronto. "This is 1,000 times smaller than the tissue samples required" by other methods, she said. For their report, the technique was tested on breast tissue from two postmenopausal breast cancer patients.

Estrogen concentrations are not routinely measured because doing so with conventional methods requires large samples, the researchers noted in their report. But they said that a simpler measuring technique would, for instance, allow doctors to monitor treatment with aromatase inhibitors routinely given to breast cancer patients to block estrogen.

The new method should make that much easier, the researchers said, and it might be practical for other conditions that require hormone level monitoring, such as infertility. However, Wheeler said that the device and approach are still in the early stages of development. "We anticipate within the next five years a product based on this technique would be available," he said.

An American Cancer Society epidemiologist who was familiar with the report agreed that much more work is needed before the device will be ready for "prime time." Dr. Susan Gapstur, vice president of epidemiology for the society, said that the validity of the measurements needs to be assessed, but if the findings hold up, such a device could be very useful.

Typically, estrogen levels in the blood are measured, but those levels usually are lower than levels in breast tissue, she said. Breast estrogen levels can be measured by obtaining nipple aspirate fluid, but the fluid is difficult to obtain, especially from older women, Dr. Gapstur explained.

* * *


A test to determine whether a person's heart is healthy enough for a KIDNEY TRANSPLANT is safer than previously thought, according to a British study.

Chronic kidney disease can contribute to the development of heart disease, which means that doctors need to closely monitor the heart health of chronic kidney patients. But many doctors are reluctant to use coronary angiography -- which uses dyes and X-rays to provide an image of the inside of the heart's arteries -- on people with chronic kidney disease because of fears that the procedure raises the risk for complications.

But the study found that coronary angiography does not cause a decline in kidney function in people with advanced chronic disease and can help doctors decide when to schedule someone for a kidney transplant, said Dr. Nicky Kumar, of the Imperial College Kidney and Transplant Institute in London, and colleagues.

They looked at 76 people with late-stage chronic kidney disease who were potential transplant recipients. Kidney function tests were recorded a year before and a year after they had coronary angiography. Kidney function was similar before and after the procedure, indicating that it didn't harm the kidneys.

Coronary angiography detected coronary artery disease in 23 people, which meant they couldn't have a kidney transplant until their heart problems were treated. The heart testing showed that 22 of them were healthy enough to have a kidney transplant instead of going on dialysis.

The researchers said this kind of heart health information is essential for optimal care because having a kidney transplant before someone needs dialysis is the most effective treatment for chronic kidney disease.

The study was published in the Clinical Journal of the American Society of Nephrology.

* * *

The information in the following story mirrors my own experience with chemo, so it's good to be able to pass this on 'con brio':


Cancer Chemo Less Exhausting for Patients Getting Intense Exercise

Cancer patients undergoing chemotherapy feel less exhausted if they enroll in an intense program that exercises the mind as well as the body, according to a recent Danish study.

Earlier studies showed that both moderate exercise and psychosocial programs can help. The question became, Could both kinds of programs be combined -- and intensified -- for greater impact?

To find out, Lis Adamsen, PhD, and colleagues at Copenhagen University Hospital, Denmark, asked 269 adult cancer patients to enroll in a nine-hours-a-week exercise program for six weeks. Half the volunteers were randomly assigned to a control group and were asked to wait six weeks to join the program.

Although the program was designed to appeal to men and women, women were much more likely to volunteer. In the end, 196 women and 73 men volunteered for the study; 235 of them completed the program.

The program included:

Monday, Wednesday, and Friday: High-intensity physical training (30 minutes of warm-up, 45 minutes resistance training, and 15 minutes of cardiovascular training).

Tuesdays: 90 minutes of body-awareness training (stretching on week 1, yoga breathing on weeks 2-3, and Pilates movement on weeks 4-6).

Monday, Tuesday, Wednesday, and Friday: 30 minutes of relaxation training to follow physical training or body-awareness training.

Monday and Friday: 30 minutes of massage

Patients weren't allowed to pick and choose -- they had to show up for the entire program, regardless of how they felt after their chemo treatments.

One patient with a brain tumor had a seizure after cardio training, so Adamsen and colleagues warn brain cancer patients not to try this kind of exercise. Ill effects were not seen in other patients. Instead, those completing the program felt better. Although improvements were small to medium in size, the exercise program significantly reduced fatigue and increased patients' sense of vitality. They felt fewer limits in their daily activities than did patients who did not exercise.

"The range of exercise components used ... has been shown to be feasible, safe, and beneficial to various patients with cancer during chemotherapy -- even patients with advanced disease," Adamsen and colleagues conclude.

They note, however, that a program with more appeal to men needs to be developed.

* * *


Helps Improve Nervous System Function in Multiple Sclerosis Patients

A new drug for multiple sclerosis truly helps some patients walk better, according to an FDA advisory panel. The finding, by a panel of outside experts, makes it more likely that full FDA approval will come soon. If approved, the drug -- tentatively named Ampriva -- would be the first to improve nervous system function in people suffering from the disease.

Current treatments slow MS progression and target symptoms, but they do not affect the damage the disease already has done. Nerves frayed of their protective myelin sheath lose their ability to send electrical signals. Ampriva improves conduction of nerve signals.

Nerve damage is among the symptoms that most bother people with MS, often making it very difficult for them to walk. In clinical trials, over 35% of MS patients taking Ampriva were able to walk faster, says Andrew D. Goodman, MD, director of the multiple sclerosis center at the University of Rochester and the lead investigator in the clinical studies.

"Those who responded improved walking speed on average by 25%," said Goodman. "This can mean things like getting to the bathroom on time before having an accident, or getting across the street before the light changes."

While Ampriva can help even patients with relentlessly progressive MS, patients do continue to get worse over time. And the improvements seen with the drug are rather modest. In fact, the central question the advisory panel was asked to decide was whether the improvements were truly significant to patients.

At the hearing, people with MS and their family members told the panel that they would welcome the kind of improvements seen in the clinical trials. Goodman says he hears the same thing from his patients. "The kinds of things that people have described to me are, 'Look, I can get around the supermarket without having to hold on to the cart all the time,' or 'Just getting up that step between the garage and the house gives me independence,'" he says.

The drug is not risk-free. It is a new formulation of a drug called fampridine, which was originally used as a bird poison. Some 20 years ago, test tube studies suggested that fampridine could improve nerve conduction. Since then, some neurologists -- Goodman is not one of them -- have ordered the drug from compounding pharmacies for their MS patients.

Fampridine causes seizures and convulsions at doses not much higher than the dose thought to be therapeutic. The sustained-release formulation of fampridine used in Ampriva lessens the chance of this side effect, but the drug cannot be used by MS patients with a history of seizures.

The FDA advisory panel voted 10-2 (with one abstention) that -- for some MS patients -- they would consider the benefits of Ampriva to outweigh the risks.
* * *

One of the good side effects of the health care conversations taking place over the past several months, is the plethora of health-related stories appearing in media that ordinarily carries far fewer such pieces. Here's a good one, appearing October 18 in The New York Times:


By Natasha Singer

Time to revisit the always compelling - and often disconcerting - debate over digital privacy. So, what might your movie picks and your medical records have in common?

How about a potentially false sense of control over who can see your user history?

While Netflix and some health care concerns say they have been able to offer study data to researchers stripped of specific personal details like your name, phone number and e-mail address, in some cases researchers may be able to re-identify you by correlating anonymous information with the digital trail that you've left on blogs, chat rooms, and Twitter.

Of course, you may be fine with that. On the other hand, you may not want complete strangers rummaging around in your history of movie selections or medical needs.

For example, contestants in Netflix's competition to improve its recommendation software received a training data set containing the movie preferences of more than 480,000 customers who had, as they say in the trade, been "de-identified." But as part of a privacy experiment, a pair of computer scientists at the University of Texas at Austin decided to see if it was possible to re-identify those unnamed movie fans.

By comparing the film preferences of some anonymous Netflix customers with personal profiles on, the Internet movie database, the researchers said they easily re-identified some people because they had posted their e-mail addresses or other distinguishing information online.

Vitaly Shmatikov, an associate professor of computer science at the University of Texas at Austin and a co-author of the "de-anonymization" study, says the researchers were able to analyze users' public postings and connect that to their Netflix preferences - including how a person may have rated films with controversial themes. Those are choices a person may or may not want to make public, Mr. Shmatikov said.

Steve Swasey, a Netflix spokesman, disputed the study's conclusions, saying the customers were not-re-identifiable because Netflix had altered the data set before sending it to contestants.

"There is no way with certainty that anyone could link a Netflix member with the data Netflix has disclosed by linking it with any publicly available data," he said. "The anonymity of the information is comparable to the strictiist federal standards for anonymizing personal health information."

Nevertheless, the Texas researchers say they were indeed able to positively identify Netflix customers, and some privacy advocates say their study raises questions about whether newly strengthened laws governing the security of electronic health records -- which contain information on diagnoses and treatments entered by health care providers -- may offer incomplete privacy protection. Leaked movie preferences might embarrass or stereotype you, they said. But information extracted from medical records and then linked back to you, they said, had the potential to cause social, professional and financial harm.

"Movie records can be sensitive in some cases; it could be embarrassing for someone to find out I like romantic comedies," Mr. Shmatikov, the computer scientist, said in a recent phone interview. "But definitely for health records, this is a huge issue."

And you don't need records containing a person's name and address to figure out to whom the records belong, he said, "As our research shows, pretty much any information that distinguishes one person from another can be used to re-identify records."

The idea of an entirely paperless medical system holds the promise of more efficient and cost-effective care. And, with the incentive of stimulus package money, many companies are rushing to sell clinical information systems to streamline services like patient scheduling, sample tracking, and billing at hospitals and clinics.

The clinical information systems market in the United States has sales of $8 billion annually, and about 5 percent of that comes from data and analysis, according to estimates by George Hill, an analyst at Leerink Swann, a health care investment bank.

But by 2020, when a vast majority of American health providers are expected to have electronic health systems, the data mining component alone could generate sales of up to $5 billion, Mr. Hill said. Demand for the data is likely to be robust. Policy makers and hospitals will want to dig into it to analyze physician practices and glean information about patient health trends.

Big players like the Cerner Corporation, which maintains electronic health systems for 8,000 clients, including large hospitals and retail clinics, and smaller players like Practice Fusion, which offers its Web-based health record systems free to health care providers, say they make use of patient data collected from their clients.

A spokeswoman for Cerner, whose Web site promotes its "data mining of our vast warehouse of electronic health records," said the company shares de-identified patient data with researchers or drug companies looking for patients to participate in clinical trials. The patient records are "double scrubbed," she said, explaining that the company removes personal data like names and addresses before it runs a search using a numbered code for each patient.

Other sensitive information, like mental health records, might be removed before the patient data is sent out, she said.

The Web site of Practice Fusion, meanwhile, quotes Ryan Howard, the chief executive, as saying that the company subsidizes its free record-keeping systems by selling de-identified data to insurance groups, clinical researchers and pharmaceutical companies, in an interview, however, Mr. Howard said Practice Fusion had not yet started selling patient information but that it intended to do so.

New regulations require notifying patients if their personally identifiable medical information gets loose, and they prohibit selling protected health records. But privacy advocates said electronic health records remain vulnerable because no federal law now forbids the sale of de-idenfitied health care data.

In 1997, for example, a researcher identified the medical records of William Weld, then the governor of Massachusetts, by correlating birthdays, ZIP codes and gender in voter registration rolls and information published by the state's government insurance commission.

There are no current federal laws against re-identification, said Dr. Deborah Peel, a psychiatrist who is a director of Patient Privacy Rights, a nonprofit watchdog group in Austin, Tex.

"Once personal health data gets out there, it's like the Paris Hilton sex tape," Dr. Peel said. "It's going to be out there forever."

* * *


Studies Show TNF Blockers May Raise Risk of Non-melanoma Skin Cancer

People who take immune-disease drugs called TNF blockers for RHEUMATOID ARTHRITIS should check their bodies regularly for abnormal growths that can signal skin cancer.

That's the advice of doctors after two new studies showed that patients treated with TNF blockers have higher rates of skin cancer than patients who take other disease-modifying anti-rheumatic drugs, or DMARDs.

TNF blockers include Remicade, Enbrel, Humira, Cimzia, and Simponi. They neutralize a protein, tumor necrosis factor alpha, that is overproduced in inflammatory diseases like rheumatoid arthritis. TNF, however, also has a normal function in the body: fighting cancer. The FDA already requires that TNF-blocking drugs carry a boxed warning of an increased risk of cancer.

The new studies link the drugs to skin cancer in particular and quantify "what we already suspected," says Eric Ruderman, MD, a rheumatologist at Northwestern University who was not involved in the new studies. Still, experts stress that the overall risk of developing skin cancer is low and that for most patients with rheumatoid arthritis, the benefits of TNF blockers outweigh the risks.

"Yes, the findings give us pause, but TNF blockers have helped many patients ravaged by rheumatoid arthritis to become ambulatory," says Johns Hopkins rheumatologist Allan Gelber, MD.

TNF Blockers and Skin Cancer

For the first study, researchers at Washington University in St. Louis combed the medical records of nearly 17,000 people with rheumatoid arthritis treated at VA hospitals around the country. About 3,000 of them were treated with TNF blockers.

Compared with people treated with other DMARDs such as Rheumatrex or Arava, people taking TNF blockers were 34% more likely to develop nonmelanoma skin cancer. The drugs were also associated with a slightly higher risk of malignant melanoma. The longer a person was on TNF blockers, the greater their risk of non-melanoma skin cancer, says Prabha Ranganathan, MD, a rheumatologist at Washington University.

Men, older patients, and those who took steroids to control their disease were also at increased risk of developing non-melanoma skin cancer.
"Older patients with rheumatoid arthritis on anti-TNF therapy need to be watched closely for the development of skin cancer, especially if they are male, have been on these treatments for a long time, and have a history of other cancers," she said.

British Study on TNF Blockers

For the second study, British researchers reviewed a national registry that tracks the progress of people with rheumatoid arthritis. Taking a TNF-blocking drug appeared to increase the risk of developing non-melanoma basal or squamous cell skin cancers by about 70%, compared to treatment with a traditional DMARD, but the finding could have been due to chance.

Further analysis showed that not all TNF blockers posed an equal risk. In particular, Remicade was associated with a significant threefold increased risk of skin cancer compared with DMARD treatment.

"One possible reason may be that because people go to the hospital to get Remicade, which is given as an infusion, they're around health care providers more often and therefore it's more likely that their cancer would be found," says Kimme Hyrich, MD, senior lecturer in rheumatic disease epidemiology at the University of Manchester, England.

The bottom line: People on TNF blockers should be get regular skin exams and report any unusual changes, such as moles or new lesions, to their doctors immediately.

Researchers also reported that rheumatoid arthritis patients who are taking TNF blockers appear to be at increased risk of septic arthritis -- an infection of the joints. "The risk about doubles when compared to patients receiving treatment with other disease-modifying drugs," says Deborah Symmons, MD, professor of rheumatology and musculoskeletal epidemiology at the University of Manchester, England. The study involved 11,757 people with RA who were taking TNF blockers and 3,515 patients taking other DMARDs.

Symmons said she attempted to adjust for other factors that raise the risk of infection -- including that patients on TNF-blocking medications tend to have more severe rheumatoid arthritis than patients treated with other drugs. "However, that still left us with a residual additional risk associated with anti-TNF agents."

* * *

See you next month ...

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

Elaine Jesmer

back to newsletter archive


Home | About Elaine | About the Book | Mission | | Chemotalk Newsletter | Media Room |
Chemo Coaching | Speaking Engagements | Blog | Links | Contact