Chemotalk Newsletter

Chemotalk Newsletter, Vol. 38: June 1, 2011

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I want to start this month with a piece written by a nurse.  She is Theresa Brown, a contributor to The New York Times' "Well" blog, and I've spread her words on this newsletter in the past.

But first, I want to say a few words about nurses.  Since being treated for cancer, my appreciation for these men and women has grown beyond admiration, to close to reverence.  Far more than doctors, nurses work in the trenches, where illnesses and the devastation they wreck on us play out in real time. As much as I love and appreciate my doctors, it's the nurses I want to hang out with, especially when I want an opinion.  I understand why doctors are loathe to say anything that could lead to a lawsuit, so I instinctively turned to my wonderful oncology nurse when, for example, I wanted a real answer to what "terminal" looks like.  He didn't pull any punches.  He never does, and I've made him promise that when it comes to my future health, he never will.  He, and the others he works with, may never be elected Cure Magazine's "Nurse of the Year".  But they have our love, because we know they have our backs.

PHYSICIAN, HEAL THYSELF

By Theresa Brown

It was morning rounds in the hospital and the entire medical tam stood in the patient's room.  A test result was late, and the patient, a friendly, middle-aged man, jokingly asked his doctor whom he should yell at.

Turning and pointing at the patient's nurse, the doctor replied, "If you want to scream at anyone, scream at her."

This vignette is not a scene from the medical drama "house", nor did it take place 30 years ago, when nurses were considered subservient to doctors Rather, it happened just a few months ago, at my hospital, to me.

As we walked out of the patient's room I asked the doctor if I could quote him in an article.  "Sure," he answered.  "It's a time-honored tradition - blame the nurse whenever anything goes wrong."

I felt stunned and insulted.  But my own feelings are one thing; more important is the problem such attitudes pose to patient health.  They reinforce the stereotype of nurses as little more than candy stripers, creating a hostile and even dangerous environment in a setting where close cooperation can make the difference between life and death.  And while many hospitals have anti-bullying policies on the books, too few see it as a serious issue.

Today nurses are highly trained professionals, and in the best situations we form a team with the hospital's doctors.  If doctors are generals, nurses are a combination of infantry an aides-de-camp.

After all, patients are admitted to hospitals because they need round-the-clock nursing care.  We administer medications, prep patients for tests, interpret medical jargon for family members and double-check treatment decisions with the patient's primary team.  Nurses are also the hospital's front line: we sound the alert of a patient takes a serious turn for the worse.

But while most doctors clearly respect their colleagues on the nursing staff, every nurse knows at least one, if not many, who don't.

Indeed, every nurse has a story like mine, and most of us have several. A nurse I know, attempting to clarify an order, was told, "When you have 'M.D.' after your name, then you can talk to me."  A doctor dismissed another's complaint by simply saying, "I'm important."

When a doctor thoughtlessly dresses down a nurse in front of patients or their families, it's not just a personal affront, it's an incredible distraction, taking our minds away from our patients, focusing them instead on how powerless we are.

That said, the most damaging bullying is not flagrant and does not fit the stereotype of a surgeon having a tantrum in the operating room.  It is passive, like not answering pages or phone calls, and tends toward the subtle: condescension rather than outright abuse, and aggressive or sarcastic remarks rather than straightforward insults.

And because doctors are at the top of the food chain, the bad behavior of even a few of them can set a corrosive tone for the whole organization. Nurses in turn bully other other nurses, attending physicians bully doctors-in-training, and experienced nurses sometimes bully the newest doctors.

Such an uncomfortable workplace can have a chilling effect on communication among staff.  A 2004 survey by the institute for Safe Medication Practices found that workplace bullying posed a critical problem for patient safety: rather than bring their questions about medication orders to a difficult doctor, almost half the health care personnel surveyed said they would rather keep silent.  Furthermore, 7% of the respondents said that in the past year they had been involved in a medication error in which intimidation was at least partly responsible.

The result, not surprisingly, is a rise in avoidable medical errors, the cause of perhaps 200,000 deaths a year.

Concerned about the rule of bullying in medical errors, the Joint Commission, the primary accrediting body for American health care organizations, has warned of a distressing decline in trust among hospital employees and with it, a decline in the quality of medical outcomes.

What can be done to counter hospital bullying?  For one thing, hospitals should adopt standards of professional behavior and apply them uniformly, from the housekeepers to nurses to the president of the hospital.  And nurses and other employees need to know they can report incidents confidentially.

Offending parties, whether doctors or nurses, would be required to undergo civility training, and particularly intransigent doctors might even have their hospital privileges -- that is, their right to admit patients -- revoked.

But to be truly effective, such change can't be simply imposed bureaucratically.  It has to start at the top.  Because hospitals tend to be extremely hierarchical, even well-meaning doctors tend to respond much better to suggestions and criticisms from people they consider their equals or superiors.  I've noticed that doctors otherwise prone to bullying will tend to become models of civility when other doctors are around.

In other words, alongside uniform, well-enforced rules, doctors themselves need to set a new tone in the hospital corridors, policing their colleagues and letting new doctors know what kind of behavior is expected of them.

`This shouldn't be hard: most doctors are kind, well-intentioned professionals, and I rarely have a problem talking openly with them.  But unless we can change the overall tone of the workplace, doctors like the one who insulted me in front of my patient will continue to act with impunity.

I wish I could say otherwise, but after being publicly slapped down, I will think twice before speaking up around him again.  Whether that was his intention, or whether he was just being thoughtlessly callous, it's definitely not in my patients' best interest.

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BLOOD PRESSURE MAY PREDICT KIDNEY CANCER OUTCOME

In people with advanced KIDNEY CANCER, blood pressure appears to indicate how well their medication is working, with high blood pressure linked to longer survival.  The finding comes from a study of 544 people being treated with the drug sunitinib (Sutent) for advanced kidney cancer.

The researchers found that those whose maximum systolic blood pressure reached 140 mmHg or higher survived nearly four times longer than those who had a lower maximum systolic blood pressure -- 30.5 months vs. 7.8 months. (Systolic is the top number and diastolic the lower number in a blood pressure reading.)

People who had a maximum diastolic blood pressure of 90 mmHg or greater survived twice as long as those with a lower maximum diastolic blood pressure -- 32.2 months vs. 14.9 months.

The researchers also found that progression-free survival was 2.5 to 5 times longer in people with high blood pressure -- 12.5 months for those with systolic hypertension vs. 2.5 months for those without, and 13.4 months for those with diastolic hypertension vs. 5.3 months for those without.

"These findings support the hypothesis that high blood pressure may act as a biomarker of a medication's anti-tumor effectiveness," said study leader Dr. Brian Rini, a staff physician at the Cleveland Clinic's Taussig Cancer Institute. "What that means is that physicians may be able to monitor a patient's blood pressure to gauge how effectively sunitinib is treating their advanced kidney cancer."

The study was published in the Journal of the National Cancer Institute.

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STUDY SHOWS EARLY SURGERY CUTS DEATHS FROM LOW-RISK PROSTATE CANCER

Fifteen-year results from a Swedish study show that early prostate surgery cuts deaths in under-65 men with "low-risk" PROSTATE TUMORS -- but for today's men, the definition of "low risk" has changed.  The study of 695 men with early prostate cancer assigned half the men to immediate surgery -- prostatectomy -- and half to watchful waiting. The first results, reported in 2002, showed that early surgery improved survival.

In watchful waiting, patients are not treated but monitored closely to see if there is any progression of the disease.  Now, 15 years after the study began, it's clear that men who underwent early surgery cut their risk of death from prostate cancer by 38%.

However, only men under age 65 saw this benefit. Early surgery did not significantly improve survival in men diagnosed with prostate cancer after age 65, according to Anna Bill-Axelson, MD, PhD, lead author of the report in the New England Journal of Medicine.

"What we see is that surgery reduces prostate cancer deaths, but that not all patients need to undergo surgery," said Bill-Axelson. "It depends on age, on the presence of other medical conditions, on patient preference, and on how the tumor looks. You cannot generalize and say everybody needs to undergo surgery."

The study showed that:

Overall, 15 men had to undergo prostate surgery to save one death from prostate cancer. For men under age 65, seven had to be treated to prevent one prostate cancer death.

Men whose tumors had broken through the prostate capsule had a much higher risk of death than did those with tumors that remained inside the capsule. 63% of the men assigned to watchful waiting and 40% of the men assigned to prostatectomy needed androgen-deprivation therapy, which has serious side effects that include sexual dysfunction, fatigue, and risk factors for diabetes and heart disease.

More men in the watchful waiting group than in the prostate surgery group died from causes other than prostate cancer but with spreading prostate cancer that would likely have been fatal.

Possibly the most important study finding is that among these younger men, surgery improved survival even in those with prostate tumors considered to be low risk -- by the standards of the decade 1989-1999.  "When we say the low-risk group benefits from surgery, it is not as we would define a low-risk group by today's standards," Bill-Axelson says. "It is important that people don't panic and all go for surgery. It is important to have people closely watched and to undergo surgery when necessary."

There are degrees of "low risk" for prostate tumors, says prostate cancer expert Matthew R. Smith, MD, PhD, director of the genitourinary malignancies program at Massachusetts General Hospital. Smith's editorial accompanies the Bill-Axelson study in the New England Journal of Medicine. Smith notes that in the Swedish study, 88% of the men had tumors that could be felt on a rectal exam, and only about 5% had their cancer detected via PSA screening tests. In the U.S. today, fewer than half of men diagnosed with prostate cancer have tumors that can be felt on a rectal exam, and most cancers are detected via PSA screening.  This means that today, most prostate cancers are diagnosed seven to 10 years earlier than they were when the men in the Swedish study were diagnosed.

"Since these cancers were not well represented in the Scandinavian study, we cannot generalize from this to say men diagnosed with low-grade cancer today would derive the same benefit. We still don't know if we have to treat all of those men," said Smith, who agrees with Bill-Axelson that immediate treatment isn't necessary for all of these men. When a patient's biopsy shows that a prostate tumor has a low grade, and that tumor volume is small, the patient is a likely candidate for active surveillance.

For some doctors, "active surveillance" differs a bit from "watchful waiting" in that the tumor is carefully monitored, with repeat biopsies as necessary, so that a patient gets appropriate treatment as soon as the cancer progresses -- but well before it becomes a high-risk tumor.

"We do enthusiastically recommend active surveillance in carefully selected patients," Smith says. "This is not to say, 'Have surgery or go off on your own.' It is actively monitoring men with low-risk disease and selectively intervening when there is sufficient information about the cancer to justify treatment."

Men worried about prostate cancer and the doctors who treat the disease would love to have a lot more information about prostate cancer, a better screening test, and treatments with fewer side effects. But Smith insists that treatment plans can be optimized for each patient.  "We can individualize patient decisions," Smith says. "We may not have all the information we need, but we can still make good decisions."

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In a related story:

GENETIC MUTATION LINKED TO PROSTATE CANCER IN BLACKS

Researchers have identified a mutation in a small number of black American men with a family history of PROSTATE CANCER.  This germline mutation of the androgen receptor (AR) may prove to be a genetic biomarker for familial prostate cancer in the black American male population, according to the team at Louisiana State University in New Orleans.

Black American men have a higher incidence of prostate cancer than any other racial group.

The small amount of research that's been done on the role that AR mutations play in prostate cancer has been limited to white men.

This study found a germline AR-A1675T substitution mutation in the DNA-binding domain in three black American men with a family history of early-onset prostate cancer. This mutation may contribute to prostate cancer by "altering the AR DNA-binding affinity and its response to androgens, non-androgenic steroids or anti-androgens," according to the study.

The study was published in the Asian Journal of Andrology.

Further research is needed to learn more about the role this mutation plays in prostate cancer in black Americans, the researchers said.

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STOMACH BACTERIA MIGHT TRIGGER RHEUMATOID ARTHRITIS

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 was 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, the researchers found.

"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."  She 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. "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."

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HIGH HORMONE LEVEL LINKED TO CANCER DEATH IN OLDER MEN

High levels of a hormone called insulin-like growth factor 1 (IGF-1) are associated with an increased risk of CANCER death in older men, according to a new study.

The findings, published in the Journal of Clinical Endocrinology & Metabolism, suggest that IGF-1 may prove a useful biomarker for predicting cancer risk.

IGF-1, which is similar in structure to insulin, is regulated by growth hormone. Levels of growth hormone and IGF-1 decline as men and women age and this decrease is believed to be linked to health problems associated with old age. In an attempt to counter this, some people take supplemental growth hormone to elevate levels of IGF-1, according to background information in the study.

"This is the first population-based study to show an association of higher IGF-1 levels with increased risk of a cancer-related death in older men," said study corresponding author Gail Laughlin, University of California, San Diego. "Although the design of this study does not explicitly show that the higher IGF-1 levels caused the cancer death, it does encourage more study as well as a re-examination of the use of IGF-1 enhancing therapies as an anti-aging strategy."

The study included 633 men, aged 50 and older, whose IGF-1 levels were measured between 1988 and 1991. During 18 years of follow-up, men whose IGF-1 levels were above 100 nanograms per milliliter at the start of the study were nearly twice as likely to die of cancer as those with lower levels of the hormone.

"In this study, the increased risk of cancer death for older men with high levels of IGF-1 was not explained by differences in age, body size, lifestyle or cancer history," said lead author Jacqueline Major. "If these results are confirmed in other populations, these findings suggest that serum IGF-1 may have potential importance as a biomarker for prognostic testing."

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Yes, it's a study done on mice.  But a good mouse study can - and in this case, did - lead to a study on humans:

FREEZING TECHNIQUE MAY STOP BREAST CANCER

Freezing BREAST TUMORS helped stop the spread of the cancer in mice, a new study has found.  Researchers tested two cryoablation (freezing) techniques in mice with breast cancer. Both involve applying a cold probe to the tumor, but one method involves rapid freezing (about 30 seconds) of the tumor, while the other takes a few minutes.

The mice that received cryoablation were compared to mice in which breast tumors were removed with surgery.  Both cryoablation methods killed breast tumors. Mice treated with the rapid cryoablation had fewer tumors spread to the lungs and had better survival than mice treated with the slower freezing technique or those treated with surgery alone, according to the researchers from the University of Michigan Comprehensive Cancer Center.

The better results associated with rapid cryoablation may result from changes in the immune system that help kill tumors. The slower freezing method didn't have the same effect on the immune system, the study authors found.

The study findings are published in the journal Annals of Surgical Oncology.

The researchers are currently conducting a clinical trial to test the effectiveness of rapid cryoablation in breast cancer patients. "Cryoablation has strong potential as a treatment for breast cancer," said study lead author Dr. Michael Sabel, associate professor of surgery at the University of Michigan Medical School. "Not only does it appear effective in treating the primary tumor with little cosmetic concerns, but it also may stimulate an immune response capable of eradicating any cells that have traveled throughout the body, reducing both local and distant recurrence, similar to giving a breast cancer vaccine.

"What we learned in this study is that all cryoablation is not equal," Sabel said. "The technique used to freeze the tissue can have a significant impact on how the immune system responds. The system we use today appears to be ideal for both destroying the tumor within the breast and generating an anti-cancer immune response."

Currently, cryoablation is used routinely to treat prostate cancer, kidney cancer, and a number of cancers that have spread to the liver and bones.

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Finally, from The New York Times, an opinion with which I strongly disagree. Let's just say I'm glad he's not my doctor:

DRUGS AND PROFITS

By Dr. Frederick C. Tucker, Jr.

Last year, the Food and Drug Administration rescinded approval of the drug Avastin for treating BREAST CANCER patients, prompting a firestorm of criticism.  The decision was denounced by some politicians as health care rationing, and by breast cancer patients who feared that they would be deprived of a drug that they felt had helped them immensely.

But these criticisms ignore the facts: Avastin was rejected simply because it didn't work as it was supposed to, and the FD.A. should resist the aggressive campaign by Genentech, the drug's maker, to get that ruling reconsidered at a hearing in late June.

Avastin has been on the market for seven years, and combined with other drugs it is effective in treating, but not curing, some colon, lung, kidney and brain cancers.  It inhibits the development of new blood vessels and in so doing can starve a growing tumor.

Treating a breast cancer patient with Avastin costs about $90,000 a year, and Genentech could lose $500 million to $1 billion a year in revenue if the F.D.A. upholds the ban.

A clinical trial published in 2007 demonstrated that Avastin, when paired with the chemotherapy drug Taxol, halts the growth of metastatic breast cancer for about six months longer than chemotherapy alone. Genentech then asked the F.D.A. for approval of Avastin, combined with Taxol, for use against metastatic breast cancer.

This halt in tumor growth is known as progression-free survival.  But delaying the worsening of cancer does not necessarily prolong life, and Avastin was not shown to lengthen patients' overall survival time.  So Genentech argued that the drug led not to longer life, but to improved quality of life.

In 2007, an F.D.A. advisory committee rejected the application, deciding that the toxic side effects of Avastin outweighed its ability to slow tumor growth.  The F.D.A., however overrode the committee and granted what is called accelerated approval, allowing Avastin to be used pending further study.  The criteria for full approval was that Avastin not worsen overall survival and that the drug provide clinically meaningful progressing-free survival.

To support its case, Genentech submitted data from two additional clinical trials in which Avastin was paired with chemotherapy drugs other than Taxol.  Like the first trial, neither showed a survival benefit.  Both showed an improvement in progression-free survival, though this outcome was much less impressive than in the original study.  In addition to seeking full approval for the Avastin-Taxol combination, Genentech also asked the F.D.A. To approve the use of Avastin with the drugs used in these follow-up studies.

Genentech presented progression-free survival as a surrogate for better quality of life, but the quality-of-life data were incomplete, sketchy and, in some cases, non-existent.  The best that one Genentech spokesman could say was that "health-related quality of life was not worsened when Avastin was added."  Patients didn't live longer, and they didn't live better.

It was this lack of demonstrated clinical benefit combined with the potentially severe side effects of the drug, that led the F.D.A. last year to reject the use of Avastin with Taxol or with the other chemotherapies for breast cancer.

In its appeal Genentech is changing its interpretation of its own data to pursue the case.  Last year Genentech argued that the decrease in progression-free survival was not due to the pairing of Avastin with drugs other than Taxol.  This year, however, in its brief supporting the appeal, Genentech argues that the degree of benefit may indeed vary with "the particular chemotherapy used with Avastin."  In other words, different chemotherapies suddenly do yield different results, with Taxol being superior.  The same data now generate the opposite conclusion.

Perhaps more troubling is the resort to anecdote in the brief to the F.D.A. and in the news media.  Oncologists recounted their successes, and patients who were doing well on Avastin argued for its continued approval. But anecdote is not science.  Such testimonials may represent the human voices behind the statistics, but the sad fact is that there are too many patients who have been treated with Avastin but are not here to tell their stories.

Avastin will not disappear because of the F.D.A. decision.  It remains available for treating other cancers, and research to find its appropriate role in breast cane treatment continues.  In the meantime, the F.D.A., which is expected to make its decision in September, needs to resist Genentech's attempt to have it ignore scientific evidence.

Serious progress in the treatment of cancer will not be the result of polemics, lobbying or marketing.  Genentech's money and efforts would be better spent on research for more meaningful treatments for breast cancer.

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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 jesmer_e@pacbell.net

Elaine Jesmer

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