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Chemotalk NewsletterChemotalk Newsletter, Vol. 25: May 1, 2010
Hello, again... I'm starting this month's Newsletter with an editorial that ran in a recent
issue of The New York Times. For news wonks, it should be noted that this
was the lead editorial in the Sunday paper, that has the paper's highest
weekly circulation. The Times obviously sees the importance of this issue,
probably more clearly than many medical news resources. As far as those of
us who have, or had cancer, no issue is really as important as the search
for a cure. What this piece indicates is, this part of the system is broken
and failing: FALTERING CANCER TRIALS The nation's most important system for judging the clinical effectiveness of cancer treatments is approaching "a state of crisis". That is the disturbing verdict of experts assembled by the National Academy of Sciences to review the performance of clinical trials sponsored by the National Cancer Institute. Unless the shortcomings are remedied, some of President Obama's ambitious health care reforms will be jeopardized and his audacious goal of finding "a cure for cancer in our time" will have almost no chance at all. The most shocking deficiency highlighted by the report, issued by the academy's Institute of Medicine, is that about 40 percent of all advanced clinical trials sponsored by the Cancer Institute are never completed. That is an incredible waste of effort and money, and a huge obstacle at a time when researchers are developing promising new therapies that must be rigorously tested. These large, government-sponsored studies are supposed to be the gold standard -- and very different from the narrow, occasionally biased studies sponsored by manufacturers seeking approval of the new drug. The government-sponsored trials can be invaluable in comparing one therapy against another (manufacturers rarely want to put their products up against a competitor's), combinations of therapies, or therapies for rare diseases with little commercial value. So it is especially worrying to hear the experts say that the system -- run by the Cancer Institute at the National Institutes of Health -- is so mired in cumbersome procedures that it needs to be completely overhauled. The Cancer Institute funds clinical trials primarily through 10 "cooperative groups" of experts. They generate ideas for testing new therapies and conduct the trials through networks of cancer centers and community oncology practices. More than 25,000 patients, 3,100 institutions and 14,000 patients participate each year. Yet a series of reviews in recent years found that the testing operation is mired in bureaucracy and poorly coordinated. A typical trial must navigate past dozens of overlapping reviews by different boards and agencies that must approve the original concept for the trial and then the protocol that will govern how it is conducted before the investigators can start enrolling any patients. The average time between developing the concept for a study and getting it started is about 2.5 years. The longer a study takes to get started, the more likely it is to become scientifically out of date, and the less likely it is that doctors or patients will want to participate. Other factors, including failure to pay investigators and their institutions the full costs of a trial, can also impede enrollment. And if not enough patients are enrolled, the study lacks the statistical power to generate meaningful results and cannot be completed. The Institute of Medicine panel, headed by John Mendelsohn, president of the M.D. Anderson Cancer Center in Houston, offered a range of suggestions for improving the prospects for success. It called for reducing the consolidating the number of cooperative groups, committees and reviews; increasing the money to support the trials; increasing the academic rewards to encourage researchers to run clinical trials; setting strict deadlines for each step in the process; and prioritizing the studies most likely to be successful. All that should be done even if money has to be transferred from other research activities. The need for improvement looms especially large now that the Obama administration is pouring substantial sums into "comparative effectiveness research." That is essential to helping doctors determine which treatments work well and which do not -- and holding down the cost of medical care. More than 11 million Americans are living with cancer or the prospect
that cancer may return, and 1.5 million more may get new diagnoses of the
disease this year, driving total cancer care costs above $100 billion a
year. Nearly one in four Americans are projected to die from cancer. It is
vitally important to find the best treatments for them. Repairing the
clinical trials system is critical not only for health care reform but for
the health of millions of Americans. Scientists have identified a mechanism by which certain tumor cells that become resistant to CANCER drugs can later lose that resistance. The discovery may lead to new ways to combat drug resistance in cancer patients, said the authors of the new study, published in the journal Cell. Although the existence of these drug-resistant cells has been common knowledge, scientists "now understand a little bit better how those cells work so they can attack them," said Robert Clarke, professor of oncology and physiology and biophysics at the Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C. Study senior author Jeffrey Settleman, scientific director of the
Massachusetts General Hospital Cancer Center and professor of medicine at
Harvard Medical School, said: "One of the big problems with cancer drug
therapy is acquired drug resistance. Most treatments, even ones that work,
fail over time because tumors become drug-resistant. It's been largely
assumed, and in some cases even demonstrated, that random gene changes
confer a lot of that resistance."
"There's a population of cells that's resistant but the resistance is not necessarily maintained forever," Clarke noted. "This suggests that the resistance is not genetic but could be reversible," added Settleman. Using models of drug-resistant cells, the study authors found a
subpopulation of tumor cells that managed to escape the effects of cancer
drugs even when given at levels 100 times greater than those that would kill
most cells. The authors tested a number of different drugs, including
gefitinib (Iressa), which is used to treat lung cancer, and lapatinib
{Tykerb), used to treat breast cancer. Most of the drugs were provided for
free by their manufacturers. But the cells, once removed from the "drugged" environment, gave rise to a new generation of cells that were again susceptible to the drug therapies. "Cells could randomly acquire and relinquish that drug-tolerance quality at low frequency so that any cell could potentially become drug-tolerant for a period of time, then surrender that ability," Settleman explained. This may be a way for the cells to survive as a group, with individual cells "compromising something for the good of the population," he stated. An enzyme that changes chromatin, part of the structure of chromosomes, is necessary for a cell to develop tolerance. Although there are no drugs that can inhibit this enzyme, compounds that blocked a group of related enzymes did manage to kill off the drug-resistant cells, the researchers said. "We discovered that there are inhibitors of certain chromatin-modifying enzymes that can actually selectively kill drug-tolerant cells," Settleman said. "That's where the therapeutic opportunity comes in. We showed that when you combine one of the chromatin-modifying enzyme inhibitors with [a drug] that treats most of the cells, you can wipe out most of the population." The researchers are now starting a trial to combine an enzyme inhibitor with a lung cancer drug to see if they can prevent the development of resistance. * * * More disturbing news about cancer treatment, but information cancer patients definitely need to be made aware of: CANCER FIGHT: UNCLEAR TESTS FOR NEW DRUG Dr. Linda Griffith was at a conference in Singapore in early January when she felt a lump in her breast. She assumed it was nothing - a cyst. And anyway, she had no time for it. She was returning on a Sunday night and the next Tuesday morning was leaving for a conference in Florida. But she had a mammogram, ultrasound and biopsy within hours of getting off the plane. The news was not good: she had cancer. Then the compliations began. Dr. Griffith, director of the Center for Gynepathology Research at M.I.T., had a test to see whether her tumor had extra copies of a protein, HER2. If it did, it would respond to a drug, Herceptin, which blocks the protein and stymies the tumor's growth. Drugs aimed at disabling proteins that spur cancer are, many oncologists say, the future of cancer therapies. Only a few are available now but almost every new drug under study is designed to disable cancer-fueling proteins. But these so-called targeted therapies are only as good as tests to find their protein targets. And while most patients do not yet know it, these tests can be surprisingly unreliable. Acknowledging the problem, cancer specialists on Monday announced new testing guidelines for one protein target, but as new targets are identified, the problem continues to grow. The test on Dr. Griffith's tumor was negative. Or was it? One small area of her tumor stained chocolate brown, indicating lots of HER2. The rest was a cream color, indicating no extra HER2 protein. Yet her treatment hinged on this result. A HER2 positive tumor has a bad prognosis. Herceptin can make that prognosis good, reducing the chances that the cancer will come back by 50% and reducing a woman's risk of dying by 40%. But Herceptin, costing $42,000 a year wholesale, causes flulike symptoms and also has a rare, serious side effect, severe heart damage that can even be fatal. And if a tumor does not have high levels of HER2, Herceptin would be, as Dr. Antonio Wolff, a breast cancer specialist at Johns Hopkins put it, "a toxic and expensive placebo." Dr. Griffith has come face to face with an emerging, but rarely acknowledged, problem in today's era of new cancer tests and therapies. HER2 tests, for instance, can give false-positives up to 20% of the time, wrongly telling women they need the rug when they do not. Five percent to 10% of the time the tests can falsely tell a woman that she should not take the drug, when she should. And Herceptin testing gor breast cancer is easy compared with what is coming next. Genentech, Herceptin's maker, is about to apply to the Food and Drug Administration to sell the drug to treat stomach cancer. But it is much more difficult to tell whether a stomach tumor has high levels of HER2, says Krysta Pellegrino, a company spokeswoman. Breast cancers usually are all positive or all negative. Not stomach cancers, which almost always have sections that are positive for HER2 and sections that are negative. The HER2 tests are the same, but "the interpretation and scoring are different," Ms. Pellegrino said. That sort of mosaic pattern is typical of cancers other than breast cancer, says Dr. Jeffrey Bloss, vice president, North American Medical Affairs at GlaxoSmithKline. And it raises questions of what a test result means. "The science is still evolving," Dr. Bloss said. "What was true last year may not be true this year." Like the HER2 tests, other molecular tests for breast cancer also have
problems. Those tests, for estrogen receptors on breast cancer cells,
determine whether cancer will be thwarted by drugs that deprive tumors of
estrogen. They can be wrong at least 10% of the time. Some
estrogen-depleting drugs, while generally safe, increase the risk of
osteoporosis and, depending on the drug, can also cause joint pain and
increase risks of stroke and cancer of the uterine lining. "How do you know they are the same?" Dr. Perez asked. "If you do the
test in two different labs, you can get two different answers."
"This is an issue that transcends breast cancer," Dr. Wolff said. "A
poorly developed test is potentially as dangerous as a poorly developed
drug."
Meanwhile, Dr. Griffith's doctor, Eric Winer at the Dana-Farber Cancer Institute, had a gradual awakening. "In my naïve view, which wasn't so many years ago," Dr. Winer said, "I thought HER2 was a switch that turns on or off and it was pretty easy to tell when it's on or off. It turns out that it is not nearly as straightforward for a large number of tumors." Now, recognizing the problem, Dr. Winer had Dr. Griffith's tumor retested with a different method, hoping the result would help him an Dr. Griffith figure out whether she could benefit from Herceptin. And Dr. Griffith was left facing the uncertainties of cancer medicine. "Me as a scientist says it's very interesting," she said. But, she said, as a patient she sees it differently. "It's really hard to know what to do." The two large national studies of Herceptin for women with HER2 positive early-stage breast cancer were just starting in 2001 when Dr. Perez, of the Mayo Clinic, a principal investigator, had a moment of truth. Women were having HER2 tests at a variety of places -- community hospitals, major medical centers, national labs. Dr. Perez decided to retest tumors in a central lab to confirm the results. The outcome stunned her and her colleagues. Twenty percent of the first 119 women whose initial tests indicated their tumors had excess HER2 turned out not to have on retesting. "We all felt, 'Oh boy, we have a problem,'" said Dr. Wolff, a study investigator. "This was huge." So the studies were modified to require central labs to retest all the tumors. Yet the discordance remained -- one-sixth of women told by local labs that they were HER2 positive were not on retesting. "We were all horrified," said Dr. Elizabeth Hammond, a pathologist at Intermountain HealthCare in Utah. The result of that moment of horror was HER2 testing guidelines by the College of American Pathology and the American Society of Clinical Oncology, dictating criteria for declaring a test positive or negative and requiring proficiency testing, among other things. In a way, the effort was a huge success. About 900 of the nation's
estimated 1,500 labs agreed to follow the guidelines. But even so, said Dr.
Bloss of GlaxoSmithKline, there seemed to be approximately a 20% discordance
between labs. GlaxoSmithKline makes Tykerb, which also focuses on HER2. Twelve years after Herceptin was approved for women with advanced breast
cancer, "we're still trying to refine the testing," said Ms. Pellegrino of
Genentech. The College of American Pathologists wants to develop testing guidelines for every molecular target for cancer drugs. It recently released new guidelines for estrogen receptor testing. And Dr. Hammond has become driven to make sure pathologist know about and follow the HER2 guidelines. At pathology meetings, she asks her audience how many know about the guidelines and are following them. "Almost everyone raises their hand," Dr. Hammond said. "I am preaching to the choir. They chose to come to the meeting. It's the ones who did not choose to come that I am worried about." But even the best labs can differ, as some women learned. When Sheila Maloney had breast cancer surgery in October, her doctor wanted to test her tumor for HER2. "I had never heard of it," said Mrs. Maloney, a 64-year-old hostess at an Oliver Garden restaurant in Lady Lake, FL. She is now seeing Dr. Perez, and ended up having her tumor tested four times with four different commonly used HER2 tests. The first test was positive, the second negative, the third positive, the fourth negative. Dr. Perez recommended that Mrs. Maloney take Herceptin. As for Dr. Griffith, the two tests for HER2 turned out to agree, but with that mixed result, it was hard to know what to do. Her tumor was on the fence -- part negative, part weakly positive. Medical experts say there are no easy answers. For now, their best advice is for women to ask that their breast cancer tissue be sent to experienced labs that follow accredation procedures like those recommended by the College of American Pathologists. But Dr. Griffith did all that. And Dr. Griffith, a scientist whose own research involves the HDR2 protein, also read and examined the literature on HER2 to prepare for a discussion with Dr. Winer. "Here I sit as a patient. My situation is ambiguous," Dr. Griffith said. In the end, the studies, along with Dr. Winer's clinical perspective, did not convince her that the drug would help. The risk of serious heart damage and other side effects was scary. And, she said, she cannot ignore the drug's price, even though her insurer would pay. Dr. Griffith decided not to take Herceptin, but she is having standard chemotherapy. "I am very comfortable with my decision," she said. * * * F.D.A. APPROVES 'VACCINE' THAT USES IMMUNE SYSTEM TO FIGHT PROSTATE CANCER The Food and Drug Administration approved the first treatment that uses
a so-called cancer vaccine, a drug that trains the body's own immune system
to fight the disease. Getting the immune system to attack cancer has tantalized scientists for decades, because it promises to have fewer side effects than the harsh chemotherapy now used. But until now the approach has yielded little but disappointment. "The big story here is that this is the first proof of principle and proof that immunotherapy works in general in cancer, which I think is a huge observation," said Dr. Philip Kantoff, chief of solid tumor oncology at the Dana-Farber Cancer Institute in Boston and the lead investigator in Dendreon's largest clinical trial for the drug. Provenge has become a cause celebre among some patients. When the F.D.A. Declined to approve the drug three years ago, some prostate cancer patients and investors protested. "I think it's fair to say that people are waiting for it," said Jan Manarite, who runs the telephone help line in Florida for the Prostate Cancer Research Institute, a patient advocacy group. Some patients may be disappointed, however, because the company said it could produce enough vaccine to supply only 2,000 patients in the next year. Dendreon and Provenge would be available at first only in the 50 centers that participated in the clinical trials. But manufacturing capacity will be expanded greatly in the coming year. Provenge is personalized for each patient. The patient's white blood cells are collected through a process often used for blood donations, and certain immune cells are separated out. The cells are then incubated with a protein often found on prostate tumors, combined with an immune system booster. The treated cells are then infused back into the patient three times over the course of a month. A full treatment will cost $93,000. Dendreon officials defended that price, saying it was in line with those of other cancer drugs in terms of cost per extra month of life provided by the drug. Men with prostate cancer typically have either radiation treatment or surgery to remove the prostate gland, followed by drugs that reduce the levels of the hormone testosterone, which fuels prostate tumors. Provenge was approved for men whose cancer has spread in the body and for whom the hormone-deprivation drugs no longer work but who still have minimal symptoms, or none at all. The only approved treatment for these men before Thursday was the chemotherapy drug Taxotere, also known as docetaxel, which in clinical trials extended lives by aout two or three months. In the largest clinical trial of Provenge, involving 512 men, those who got Provenge had a median survival of 25.8 months after treatment, while those who got a placebo lived a median of 21.7 months. After three years, 32% of those who got Provenge were alive, compared with 23% of those who got the placebo. The main side effects were fever, chills, fatigue and pain. Doctors expect that Provenge might be used before Taxotere because it has fewer side effects. Many patients do not start on chemotherapy until their symptoms, mainly bone pain, have become obvious. Provenge is the first approved product for Dendreon, which was founded in 1992 by two professors at Stanford, Dr. Edgar Engleman and r. Samuel Strober. Dendreon executives said the company had spent about $1 billion developing Provenge. David Miller, chief executive of Biotech Stock Research, predicted that sales of Provenge would reach $1 billion annually within two or three years. Dendreon's stock rose 27% to %50.18, more than double its level a year ago. Dendreon hopes to use the same technique to make other cancer accines,
including one for bladder cancer. There are dozens of other cancer vaccines
in development by other companies. Blood Test Would Predict Success of Multiple Sclerosis Treatment New study findings may soon revolutionize MULTIPLE SCLEROSIS treatment and diagnosis. The study strongly suggests that there are two major types of MS and that a simple blood test can tell one from the other. By itself, that would be a major finding. But that's not all. One type of MS responds to beta interferon, generally considered the best treatment. The other type does not -- and beta interferon treatment may even make it worse, finds Stanford University researcher Lawrence Steinman, MD, and colleagues. "I'm very excited about some of the implications of this," says Steinman. "The most important implication is that a simple blood test could tell us who does and does not respond to beta interferon. It could be that about 25% of patients are in the 'do not benefit' group." For patients who DO respond to beta interferon, the study raises hopes
that the drug may work better than previously thought, because the clinical
trials that proved beta interferon to be effective likely enrolled both
types of MS patients, watering down the drug's average efficacy in beta
interferon responders. Patricia O'Looney, PhD, vice president for biomedical research at the National MS Society, said the study will help researchers solve some of the mysteries surrounding MS. "No two people with MS are exactly alike in disease course and in response to therapy. Why is this? We don't understand why about 50% of people who take beta interferon don't respond well." TWO ROUTES TO MS Multiple sclerosis is an autoimmune disease caused by haywire immune responses that attack the myelin sheath protecting nerve fibers in the central nervous system. The culprits are lymphocytes called CD4 T helper cells, sometimes called the quarterbacks of the immune system. In MS, a subset of CD4 cells called Th1 cells direct an inflammatory immune response against myelin. Beta interferon dampens this signal, so it's a great help to people with MS -- at least, to those who respond to treatment. Why doesn't beta interferon always work for MS patients? A clue comes from a little known but equally devastating disease called neuromyelitis optica (NMO). In NMO, the immune system attacks nerve fibers, but it targets a protein different from myelin, says NMO researcher Michael R. Yeaman, PhD, vice chair of medical sciences at Harbor-UCLA Medical Center. NMO researchers have shown that the CD4 cells behind NMO aren't Th1 cells, but another type called Th17. Might Th17 cells cause some cases of MS? Yes, Steinman and colleagues found. First the researchers induced an MS like disease in mice using either autoimmune Th17 or autoimmune Th1 cells. Then they showed that beta interferon improved MS-like symptoms in mice with Th1-induced disease, but that the drug worsened MS symptoms in mice with Th17-induced disease. Humans, too, appear to have different kinds of MS. Steinman and colleagues tested blood samples taken before treatment from 26 MS patients. Six of the 12 patients who did not respond to beta interferon had high levels of Th17 in their blood. These patients with Th17 immune responses also had high levels of beta interferon in their blood -- before beta interferon treatment. That means one of two things:
New Hope for MS Patients "We are very excited about this kind of discovery, because there are new therapy approaches that focus on Th17 immune pathways," Yeaman tells WebMD. "We don't know the answers yet, but we are starting to see the dots on the page -- and if we can connect the dots, perhaps a new treatment or cure can emerge." People with MS are likely to see a benefit long before new treatments emerge. Blood tests already exist that can tell MS patients whether they have Th1 or Th17 disease. Those with Th17 disease can be spared having to undergo the side effects of beta interferon treatment, while those with Th1 disease can endure side effects knowing that the treatment is highly likely to work. "When first diagnosed with MS, the first question a person asks is, 'What can I expect? How bad will it be?'" O'Looney says. "It would it be great if we can identify something to say, 'This person has this makeup and 10 years from now may be OK, or that person may need more aggressive therapy." Despite their enthusiasm over the new findings, all of the experts consulted for this article caution that the new findings must be validated in large numbers of MS patients. All warn that it's too soon for patients to seek testing or to make treatment decisions on the basis of these preliminary findings. The study findings appear in the March 28 advance online issue of Nature Medicine. * * * EXPERIMENTAL MS DRUG OUTPERFORMS STANDARD TREATMENT Researchers Say Safety Concerns on Alemtuzumab Have Been Addressed Nearly 71% of people with early relapsing-remitting MULTIPLE SCLEROSIS treated with the experimental MS drug alemtuzumab showed no evidence of disease activity four years into a study, researchers report. That's twice the percentage of patients treated with the approved treatment, Rebif, says researcher Alasdair Coles, PhD, of the University of Cambridge. Importantly, some of the safety concerns that emerged earlier in the study appear to have been ironed out. According to the National MS Society, relapsing-remitting MS accounts for 85% of people who are first diagnosed with MS. The findings were presented at the annual meeting of the American Academy of Neurology. Alemtuzumab and MS: Safety Concerns Addressed Three-year results from the study, reported in 2008, also showed that alemtuzumab outperformed Rebif. But enthusiasm was tempered by the finding that nearly one in four alemtuzumab-treated patients also developed treatment-related thyroid complications. And 3% of the patients developed a potentially life-threatening autoimmune condition, which resulted in the death of one patient. Coles says that there have been no new cases of the autoimmune condition, known as immune thrombocytopenic purpura, or ITP. The rate of thyroid problems among patients treated with alemtuzumab is 28%, similar to that in the third-year review, he says. All the thyroid and autoimmune problems among the living patients have been successfully treated with standard medications, Coles says. More importantly, "we answered the big question -- that is, if a patient gets thyroid or ITP, will their MS get worse?" he says. "It won't. We showed that even if you develop thyroid or ITP, your MS will be treated more effectively with alemtuzumab than with Rebif." An expert not involved with the study urged caution. The updated
results do not "completely alleviate concerns" about the drug's safety, says
Aaron Miller MD, director of the Multiple Sclerosis Center at Mt. Sinai
Medical Center in New York City and chief medical officer of the National
Multiple Sclerosis Society. "Alemtuzumab is a very promising drug, but this
is a phase II trial. Only a phase III trial can really answer the question
of a drug's effectiveness and safety."
Alemtuzumab vs. Rebif for MS The phase II trial involved patients with early, relapsing-remitting multiple sclerosis who had not been treated with other MS drugs. A total of 110 patients were treated with standard Rebif and 220 patients were treated with alemtuzumab. Results of the four-year review showed that about 77% of alemtuzumab-treated patients were relapse-free compared with 49% treated with Rebif. Among patients who developed an autoimmune problem, the use of alemtuzumab was associated with a 78% reduced risk of relapse, compared with Rebif. But there is a caveat: "If patients got worse in the first few years, they were eliminated from the study," Coles says. Forty-two of the 110 patients in the Rebif group and 134 of the 220 patients in the alemtuzumab group were eliminated. Alemtuzumab is approved for the treatment of CHRONIC LYMPHOCYTIC LEUKEMIA (CLL). It's thought to work by targeting and destroying certain immune cells that normally protect against infection but are believed to be damaged in MS and other autoimmune diseases, resulting in the destruction of healthy tissue. * * * People with diabetes are at increased risk for developing some cancers and are more likely than nondiabetics to die of cancer. Now a study reports that they also have a higher risk of dying in the weeks just after cancer surgery. The analysis of 15 earlier studies encompassed about 60,000 patients, both with and without diabetes, who underwent surgery for cancers o the colon, esophagus, liver, lung, stomach, pancreas and prostate. It found that the patients with pre-existing diabetes were 50 percent more likely than nondiabetic patients to die within a month of surgery, regardless of the type of cancer. The patients inn the studies had both types of diabetes, though Type 2 is more common. Their higher death rate may have resulted from problems associated with the chronic illness, like a greater risk of infections and heart disease, said Hsin-Chieh Yeh, assistant professor of medicine and epidemiology at Johns Hopkins School of Medicine and an author of the paper, published in the April issue of Diabetes Care. "The implication of this is that diabetes care is important on top of
the cancer care," Dr. Yeh said. "When patients are diagnosed with cancer,
the patient and the family and the physician think, 'This is serious -- we
have to take care of the cancer part first.' And sometimes they forget about
the diabetes they have."
* * * Blacks are hit the hardest when it comes to both developing and dying from LUNG CANCER. A new report from the American Lung Association paints a grim picture of how environmental factors, biological factors, cultural attitudes and biases in the health-care system conspire to make this deadly disease even deadlier among members of this minority group. "Despite lower smoking rates, African-Americans are more likely to develop and die from lung cancer than whites. African-Americans are more likely to be diagnosed later when the cancer is more advanced. Also, African-Americans are more likely to wait longer after the diagnosis to receive treatment or perhaps to refuse treatment and to die in the hospital after surgery," said Dr. William J. Hicks, professor of clinical medicine at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. Black men bear an even more disproportionate share of the burden, being 37% more likely to be diagnosed with lung cancer and 22% more likely to die of the disease than white men. Only 12% of blacks will be alive five years after their lung cancer diagnosis, compared with 16% of whites, the ALA report notes. The report points to a number of factors that could explain the disparity, including differences in socioeconomic status, big business behavior and environmental exposure. For instance, thanks to concerted marketing efforts by the tobacco industry, blacks have higher rates of smoking menthol cigarettes than other groups. Menthol cigarettes have a higher level of cotinine, which is an indication of how much nicotine a person is absorbing. The U.S. Food and Drug Administration is expected to issue a report on the public health impact of menthol cigarettes in March of 2011. Education and income levels also play a role. Not only do these factors impact lifestyle choices and access to health care, including health insurance, but they largely determine where blacks are likely to work and live. According to one study, predominantly black neighborhoods have noticeably higher levels of air pollution than other communities. And a greater proportion of blacks work in the transportation industry, where they are exposed to diesel fumes, known to contribute to lung cancer risk. Meanwhile, blacks are less likely to have a gene variant that is targeted by a widely used cancer drug. The good news is that if individuals, regardless of race, receive equal
treatment for lung cancer, their outcomes are likely to be similar.
However, as Hicks pointed out, "the sad truth is that not all patients
receive equal treatment and for those who do not, their health outcomes are
poorer."
These problems have to do with both patient and provider attitudes. "We're looking not just at system failures but also at issues that are deeply rooted in the history, culture and beliefs of African-Americans," Hicks said. "This is not post-racial America. For people of color in the United States, race and discrimination are facts of everyday life, and clearly take a toll both mentally and with regard to one's physical health." There is, first of all, the legacy of the Tuskegee (syphilis) and other medical experiments of the past, in which blacks were exploited by the U.S. health-care establishment. That's made trust in the medical establishment an ongoing issue, the experts said. And while doctors appear less likely to funnel black patients to the right kind of specialists, blacks are more likely to refuse gold-standard treatment even when it is offered and available, they added. "This is not an issue that can be solved overnight," said Chuck D. Connor, president and CEO of the American Lung Association. "We've made progress in reducing smoking rates and exposure to secondhand smoke, but there is still much work that needs to be done." Hicks said he hoped experts and community members could arrive at a new
approach that will "hopefully render this very preventable form of cancer to
its state of 125 years ago, when it was a very rarely encountered medical
issue, primarily before the advent of widespread cigarette smoking."
MANY TERMINAL CANCER PATIENTS MAY BE OVERTREATED Researchers report that many patients with terminal CANCER don't benefit from getting radiation therapy designed to help them feel better by controlling symptoms like pain. The researchers, who reported their findings in the journal Cancer, say doctors are failing to properly adjust treatments to meet the needs of these patients. In some cases, they say, the radiation therapy is a product of undue optimism about a patient's chances of survival. "Radiation oncologists have fallen short in accurately determining the life span of terminally ill cancer patients. This has resulted in unduly prolonged radiation therapy regimens that often go uncompleted due to death or withdrawal from treatment," said study co-author Dr. Stephan Gripp, of the University Hospital Duesseldorf in Germany. Gripp and colleagues tracked 33 patients who were referred for palliative radiotherapy -- designed to help reduce symptoms -- at their hospital from 2003 to 2004. The study only included patients who died within 30 days. The researchers found that fewer than 60% of the patients finished their radiotherapy treatment, and many doctors thought patients would live longer than they actually did. Only 26% of the patients reported reduction in symptoms or pain. Gripp said doctors should find better ways to estimate lifespan for such patients, and he recommended that they give radiation therapy for a shorter period of time. * * * I like ending on a feel-good note, and this story definitely quanifies: BONE CANCER TECHNIQUE FOR DONGS COULD BENEFIT PEOPLE When Melissa DeWalt noticed her dog walking with a slight limp in February, she thought nothing of it. After all, Juno, her 175-pound St. Bernard, had a bad habit of running the fence with the quick-footed terriers next door. But then she saw the lump on his left front leg, and alarms went off. `DeWalt is a veterinarian. She knew it wasn't just a bruise and took Juno to her office at the VCA West Linn Animal Hospital for X-rays. The results of the X-rays started a chain of events that led to Juno becoming the first dog to undergo revolutionary treatment at a new research facility in Texas, a treatment that eventually might save the lives of children. DeWalt had a pretty good idea what the X-rays would reveal, and whe was right. On the image, the bone above the dog's wrist looked pitted; a fuzzy shadow surrounded it. A specialist she contacted agreed: it was osteosarcoma -- bone cancer. The disease is common in giant-breed dogs, says Kim Freeman, a veterinary oncologist. She sees two new cases of osteosarcoma per month, on average, nearly always in large dogs such as greyhounds, Great Danes and St. Bernards. Amputation of the afflicted limb, followed by chemotherapy to combat metastasis of cancer cells to the lungs, is the standard care for osteosarcoma, Freeman says. But Juno's care was different. DeWalt's husband, Trevor, shared his grief about Juno's diagnosis on Facebook as soon as he heard the diagnosis. His wife was not pleased about his public airing of the emotional issue at first. But the post saved Juno's leg. A St. Bernard breeder saw the Facebook message and instantly thought of a man to whom he'd once sold a dog. Stan Stearns is a lifelong fan of St. Bernards and the owner of a company that makes highly specialized equipment for medical research. So when his dog, Gabriel, was diagnosed with osteosarcoma a few years back, he did more than just see a vet. Stearns took the dog to several of the top facilities in the western U.S., speaking to the medical professionals he knew through his line of work. And he watched and learned along the way. By the time Gabriel died in 2008, Stearns knew he could improve upon the treatments available. One way to preserve a limb attacked by bone cancer, and to manage the pain that comes with it, is to apply radiation. But it's a relatively crude method: radiation weakens the already taxed bone further, making it even more susceptible to fracture. Such pathologic fracture -- fracture caused by structural weakness, rather than external impact -- means the limb has to be amputated. Stearns wanted to deliver precise, and smaller, amounts of radiation into the tumor. Working with his engineers, he developed a drill bit so small the holes it leaves are as slim as a human hair. He then set up The Gabriel Institute, a nonprofit to fund osteosarcoma treatments and research. The foundation gave money to IsoTherapeutics, which had provided an isotope for Gabriel's treatment to develop a radioactive solution to deliver into the tumor. They took an already available radioisotope called yttrium-90 and combined it with their own formula to create a compound that emits high-energy beta rays in a very limited area. Beta rays have a lot of energy but don't penetrate far. But if they're put into the center of the malignant tissue they're meant to destroy, they don't need to. Using the new drill bit, researchers injected 2 microliters -- an eye-dropper delivers about 25 times as much liquid in one drop -- of the radioactive solution into microscopic holes drilled into the cancerous bone. The scan pinpointed the cancer cells in Juno's leg. But one problem remained: Using this pinpoint method, it's important to know the tumor's boundaries, which is where someone else entered the picture. A new research facility, the Texas A&M Institute for Preclinical Studies, with Theresa Fossum at the helm, contains imaging equipment rivaled by only one other facility in the world. The institute has a 128-slice PET/CT scanner, which shows exactly where a tumor ends. On March 9, Melissa DeWalt and Juno boarded a plane from Portland, Ore. to Texas. On March 12, Fossum drilled 27 tiny holes into Juno's leg and dropped radioactive solution into each. The results of the procedure are promising: It seems to not only prevent pathologic fracture, but also the metastatic spread of tumors to the lungs. The researchers don't know why at this point. One theory -- and Fossum stresses it's pure hypothesis -- is that the cancer cells in the lung don't become active until the bone cancer cells die abruptly. This new technique kills the tumor more slowly, from the inside, which may prevent the lung cancer cells from developing. Researchers found no trace of cancer cells in Juno's lungs. OSTEOSARCOMA is most common in two populations: large dogs and young humans. The tumors found in children -- whom the disease strikes far more often than adults -- are virtually identical to those found in dogs. Before researchers can drill into a child's bone and inject it with radioactive fluid, they need to prove the method's safety and efficacy, which is usually done by creating disease in healthy animals and treating it. But Fossum is trying to convince the Food and Drug Administration that in this case real disease in animals can be a model for human applications. She would also rather help dogs that are already sick while finding ways to save human lives. That is why DeWalt only had to pay for the flight to Houston, not for the surgery or any of the care Juno received while there. When her dog arrived in Portland 10 days after the surgery, Melissa DeWalt freed Juno from the airline crate. She quickly saw how quickly the huge dog had recuperated. Juno saw DeWalt's husband on the other end of the lot and rushed toward him. All DeWalt could do was hang on to the leash as she was pulled toward their car. But she noticed the limp was gone. * * * * It can be discouraging to read "...it extended the lives of patients about
4 months compared with a placebo." Or "...in clinical trials extended lives
by about 2 to 3 months." But to patients, these numbers are virtually
meaningless, anyway. They don't reflect individual patients, which is what
people in treatment actually are. My second job out of college was in the sales promotion department of a local TV station. There, I learned the skills necessary to twist numbers into combinations that encourage advertisers to buy time on the station. I'm not great with numbers, but it wasn't rocket science. Nobody checked, anyway, as long as the station looked good. And out of that grew my skepticism about statistics, in general. Here's the quick-and-dirty about how statistics come to be. A researcher gets an idea and funding for a project. Numbers are gathered, some of them as long ago as 5 to 10 years before the study containing the statistics is finally published - first in academic journals, where it's "vetted" by peers - before it finally reaches the general public. All of this takes years. In the meantime, hundreds of new drugs that have been developed and released to treat our conditions hit the marketplace, changing or challenging the outcomes of those statistics, even as early as while the numbers are being crunched. With a few unhappy exceptions where research hasn't caught up with need yet, like pancreatic cancer or the most aggressive form of multiple sclerosis, patients are living longer. The reason I decided to post this now is because I was discussing statistics in general with a friend dealing with her cancer, when she told me a terrifying first-person story about her own oncologist, who was caught by the FDA and charged with manipulating statistics. Dubbed "Dirty Harry" by his detractors, and even more frightening than her story, the charges against him were unaccountably dropped. I'm not suggesting that statistical errors are most often produced by
design, as in the case of my friend's doctor. The majority of numbers are
just subject to manipulation, often to suit the premise of the hypothesis
the researchers are pursuing. And they're almost universally out-of-date.
Here's how we should view statistics: infrequently. And with a healthy does
of skepticism. The odds of yours, or my particular case fitting neatly into
any statistical pattern, is extremely small. Probably statistically so. * * * 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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