Chemotalk Newsletter

Hello, All...and a Happy New Year!  With any luck, the glitches in my server will have disappeared and I'll send this newsletter off without problems.  Starting off ..

I'm departing from the subject of chemotherapy for this piece, because I saw something that was wrong years ago, and it has come around again.  In 1993, I was hired by a small publisher to promote "The Silicone Breast Implant Controversy: What Women Need To Know", by Dr. Frank B. Vasey, and Josh Feldstein.  I read the book and found enough in it to scare me away from silicone implants forever.  Twelve years later, facing a double mastectomy, I tracked down Dr. Vasey and asked him if anything had changed.  He said it had not.

This story started small, a couple of days ago.  It's getting bigger.  From The New York Times:

HEALTH FEARS OVER SUSPECT FRENCY BREAST IMPLANTS SPREAD ABROAD

By Maia de la Baume and David Jolly

PARIS -- Health officials in at least a half-dozen countries are grappling with the intense anxiety of tens of thousands of women who received breast implants that were made in France with substandard silicone -- and that have been rupturing at an unusually high rates.

It is unclear whether there are health risks posed by the substandard silicone used in the implants, and the French government is expected to decide soon whether to require as many as 30,000 women in France to have their implants removed.

If the government mandates the removals, it will also pay for the procedures, though not for replacements.  Regulators will have to weigh whether the known risks associated with removing the implants outweigh the uncertain risks and anxieties associated with leaving them intact.

The British health authorities on Wednesday sought to calm women's fears, saying that there was no evidence that the suspect implants, which were manufactured by Poly Implant Prothese, a company known as PIP, had caused CANCER  They urged women who had received them to take any concerns to their surgeons but they also said, "There is currently no evidence to support routine removal" of the implants.

Britain's surgical associations also tried Wednesday to soothe anxiety.  "The message here is not to panic," said a consultant plastic surgeon, Douglas McGeorge, who spoke with the British Association of Aesthetic Plastic Surgeons.

Silicone implants have had a contentious history, with the United States imposing a 14-year moratorium on their use that ended in 2006, after years of lawsuits contending that they had caused cancer.  None of the PIP's implants appear to have been sold in the United States.

The Institute of Medicine and the Food and Drug Administration  eventually determined that there was no evidence that silicone implants were harmful.

Concerns over the silicone in the suspect implants began to build last year, when PIP was shut down and prosecutors began investigating the company for possible fraud.  The French authorities said the implants had been rupturing at a rate double the industry average, the French media reported.

But the concerns over the company's implants caught the attention of European health officials after a woman whose implant had ruptured died last month from a rare cancer called ANAPLASTIC LARGE-CELL LYMPHOMA.

The French media reported that she was the eighth woman with an implant manufactured by the company to have died of cancer, although the statistical significance of that is unclear.

French prosecutors have said that Poly Implant Prothese substituted a cheap, industrial-grade silicone for medical-grade silicone that is the industry standards.  The French authorities have said the sub-standard product causes inflammation to body tissues when implants are compromised.  But so far, they have emphasized, there is no evidence linking it to cancer.

"In case of rupture, you'd have a dangerous quantity of silicone in your body," said Laurent Lantieri, a plastic surgeon at a hospital near Paris.

Helene Guillois, 29, a nutrition student who lives in northern Franch, said she had the company's devices implanted seven years ago.

"I'm worried, because of the possible damage this could cause," Ms. Guillois said.  "No one is really capable of saying what will be the effects.  Maybe we'll see in 10 years or so.  Like all the big French medical scandals."

Breast implants, which are essentially small silicone rubber bags filled with a material, typically silicone or a saline solution, are used after breast cancer surgery or simply for cosmetic purposes.

More than 1,000 of the estimated 30,000 French women fitted with the devices have experienced ruptures or leakage.  Tens of thousands more in other countries have had the company's devices implanted, because PIP exported 80% of its products, many of them to Britain, Spain and Latin America.

More than 40,000 British women are estimated to have received the company's implants.

The implants were also used in Brazil, Argentina, Chile, Columbia and Venezuela.  In Brazil, the National Agency of Sanitary Vigilance prohibited the importation and use of the implants in April 2010, after concerns about their safety emerged in France.

Chile's Public Health Institute asked the estimated 1,000 or so women thought to have implants from the French company to contact their doctors so the implants could be removed if ruptures occurred.  Otherwise, Chilean officials asked women with the implants to undergo annual exams.

Sebastiao Guerra, the director of the Brazilian Society of Plastic Surgery, said, "We do not have significant reports of either ruptures or rejections or even cancer associated with those PIP implants, and we don't know why there is this difference with respect to the French news."

Prosecutors in Marseille have been investigating the company for possible fraud and reckless endangerment.  They say it cut costs over the last decade by using an industrial silicone gel that was not approved for medical use and that cost a fraction of the medical-grade material.

Several hundred thousand of the implants had been manufactured by the time issues were raised early last year about their quality.

Yves Haddad, a lawyer for the company's founder and chairman, Jean-Claude Mas, said there was o evidence that the product, "even if it was unapproved, is dangerous for health."

The Marseille prosecutor's office declined to comment.

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This piece, from The New York Times, brings forward a subject that can use all the attention it can get.  Obviously, it's not getting enough, or we're not speaking up enough, because it doesn't appear to be addressed, either by the industry that produces drugs, or by our government:

DRUG SCARCITY'S DIRE COST, AND SOME WAYS TO COPE

BY Roni Caryn Rabin

When Jenny Morrill, who has been battling OVARIAN CANCER since 2007, went to the hospital for her scheduled CHEMOTHERAPY treatment in June, the nurse greeted her with both good news and bad.

"She said, 'The good news is that you're doing really well on this drug Doxil.  The bad news is that we have no Doxil to give you,'" said Ms. Morrill, 55.  "My jaw dropped."

Ms. Morrill, a mother and a former arts administrator who lives near Kingston, N.Y., is one of thousands of patients with ovarian cancer, MULTIPLE MYELOMA, AIDS-related KAPOSI's SARCOMA or other cancer who were left in the lurch last summer when supplies of Doxil, a chemotherapy drug less toxic than many comparable agents, ran out because of production problems at the only plant that made it.

In recent years, about 7,000 patients in the United States were using the drug at any given time.  But by November, the factory had shut down completely.

The shortage has disrupted treatment plans and has upset patients.

"A lot of things can go wrong when you're in cancer treatment -- your white count can go down, you can become too frail to get treatment, the chemo can stop working.  One of the things you never consider is that treatment might just not be available," said Ms. Morrill, who has suffered from severe nausea since being switched to another chemotherapy drug.

"It's like you're out in the ocean and the guy on the lifeboat says, 'Sorry, they ran out of life rings.'"

Doxil is hardly the only drug disappearing from pharmacy and hospital shelves.  More than 251 drugs have been in short supply this year, including about 20 chemotherapy agents, according to the American Society of Health-System Pharmacists, which has been tracking the problem.

The vast majority are generic injectable medications widely used in hospitals, including drugs used to relieve pain, fight cancer or infections, anesthetize surgical patients, treat cardiovascular disease and manage psychiatric conditions.  Critical intravenous nutritional supplements and oral drugs for controlling diabetes, high blood pressure and attention-deficit hyperactivity disorder are difficult to find, said Cynthia Reilly, the director of practice development at the pharmacists' organization.

Roslyne Schulman, a director of policy at the American Hospital Association, said: "This is very serious.  This is a public health crisis.  The shortage cuts across all treatment categories.  It affects bread-and-butter drugs that hospitals have depended on for many years."

Nearly all hospitals in an A.H.A. survey in June reported that they had struggled with one or more drug shortages in the pervious six months, and nearly half had experienced shortages of more than 20 drugs.  Three out of four hospitals reported rationing or restricting drugs that were in short supply.

The scarcity drives up health care costs as hospitals turn to more expensive substitutes and must spend time and money teaching staff how to use unfamiliar drugs.  The risk of medical errors and complications also increases, experts say; many procedure have been delayed or canceled.

A number of complex factors have contributed to the shortages, according to Ms. Reilly, who called the situation a "perfect storm."

Recent consolidation in the pharmaceutical industry has reduced the number of factories; most of the drugs in short supply are made by just one or two companies.  That means greater repercussions when any single plant experiences production problems, cannot obtain ingredients or fails an inspection, as happened with Doxil.

Shortages often beget more shortages as health facilities stockpile supplies.  Prices often spike when unethical distributors take advantage of the panic.

Indeed, some observers have blamed manufacturers of generic drugs, suggesting that they are trying to drive up prices.  But industry representatives say their business is to sell in large quantities.

"It's to our advantage our to have shortages and to keep the products flowing," said Ralph G. Neas, the president and chief executive of the Generic Pharmaceutical Association.  "We sell affordable medications at very good prices.  We have to do more of that, not less."

Most of the missing drugs are generic simply because the vast majority of drugs in use are generic, he said.

The shortages will not be solved easily, most experts believe.  "There is no silver bullet," said Maya J. Bermingham, assistant general counsel at the Pharmaceutical Research and Manufacturers of America, a trade group.

The consequences for patients can be varied and unexpected.

While alternative drugs are usually available, they may pose hazards.    Physicians who turn to a second- or third-line drug may be less familiar with dosing and side effects.  They are often unaware of the shortages and may be caught by surprise, increasing the risk of a medical error.

The substitute drugs also may be more toxic for frail, elderly or very young patients or -- for pain medication, in particular -- take longer to work.

Second-choice anesthesia drugs can lead to longer hospital stays because patients may not wake up as quickly, said Dr. Jane C. Fitch, the vice president of the American Society of Anesthesiologists.

"For procedures that can be put off and don't have to be done right then and there, some patients have made the decision to wait and defer the surgery," Dr. Fitch said.

Substituting a brand-name drug for a generic is also likely to drive up the patient's out-of-pocket costs.

Increasingly, patients are left on their own to find the drugs they need.  Wendy Patterson, 67, who lives near Burlington, Vt., had completed four of the six Doxil treatments for a recurrence of ovarian cancer.  She was shocked when her doctor said he might not be able to provide the last two treatments.

"I immediately got on the phone when I got home and called treatment centers and hospitals near and far, large and small, to see if they would give me my last two treatments," Ms. Patterson said.  A friend in Paris helped get her into a treatment center there for the last two treatments.

She had to pick up all of the additional costs herself.  The drug shortage, she said, "is unconscionable."

But with no end in sight, experts are advising patients like Ms Patterson to take a number of practical steps.

# Have a frank conversation with your physician about recommended treatments.  Ask whether the drugs are likely to be in short supply.  Try not to let the circumstances undermine your relationship with your doctor, said Dr. Michael P. Link, the president of the American Society of Clinical Oncology.

"All of us have been blindsided by the magnitude of the shortage," he said.  "We are just as frustrated as our patients are."

# Find out if there is a waiting list for drugs you need.  Iif you and your physician are developing a new treatment plan, don't be shy about suggesting alternatives.  Check with your insurer about additional costs, if any.

# Resist the temptation to buy drugs on the Internet or from unknown sources.  Experts say counterfeit drugs not only may lack therapeutic benefit but also may be harmful.  Most drugs unavailable in the United States are not available elsewhere, either.  The Food and Drug Administration has been importing a few that are.*

If you find a source abroad for a medication, you must import it through the agency's personal importation program.  For more information, visit www.fda.gov/ForIndustry/importProgram/um173751.htm.

# Update your medical history, and be sure your doctor has all the information needed to make drug substitutions.  Get clear information about the risks and benefits of any new drug and what side effects to expect.  Disclosure about past substance abuse is wise if pain medication is being discussed.

"The patient's part," Dr. Fitch said, "is to tell us absolutely everything about every medical problem they have and every medication they take, including every drug they may buy over the counter.  All of these have interactions and impact our choice of treatment."

# The Preserving Access fo Life-Saving Medication Act, pending in a Congressional committee, would require prescription drug makers to give the F.D.A. early notification of any event likely to cause a drug shortage.  Contact your local representatives and patient adocacy organizations to learn more.

To find out more about shortages of specific drugs, visit www.fda.gov/Drugs/Drug-Safety/DrugShortages/ucm050792.htm or www.ashp.org/shortages.

* Editor's note: Let's do more than hope that manufacturers and the F.D.A. don't turn to countries with lax or no ethical standards, to take up the slack.

* * *

GAME-CHANGING BREAST CANCER NEWS

By John Carroll

Roche and Novartis have released new data on two treatments that promise to fundamentally reshape the way the majority of BREAST CANCER patients are treated.  Roche's pertuzumab, combined with Herceptin and chemotherapy checked tumor development for a median of slightly more than six months--from 8.5 months to 12.4 months. And Novartis's Afinitor demonstrated a four-month delay in disease progression among metastatic patients.

"These are two new therapies, targeted therapies, that will change the standard of care for women with metastatic disease," Jose Baselga, chief of oncology at Massachusetts General Hospital and a lead author for both studies. "They are elegant, they are hypothesis-driven and they are working through well-known mechanisms."

Afinitor is already approved for other cancers. But it was the experimental pertuzumab that offers a second pathway to managing HER2-positive breast cancer, which is present in about one in four cases. "These are among the most significant findings in drugs for metastatic cancer in the past five years," says Dana-Farber's Eric Winer.

But Roche and Novartis still have a ways to go before they complete their case on breast cancer. The gold standard for cancer data is an overall survival rate, and investigators are still piecing that picture together. Roche has already filed for an approval of pertruzumab in Europe and is expected to file soon in the U.S.

* * *

GENETIC CLUE TO MS IDENTIFIED

A rare genetic variant which causes reduced levels of vitamin D appears to be directly linked to MULTIPLE SCLEROSIS, British and Canadian researchers say.

Oxford University researchers along with Canadian colleagues at the University of Ottawa, University of British Columbia and McGill University identified the mutated gene in parents of 35 children with MS and in each case the child had inherited the gene.  Although the exact cause of MS, an inflammatory disease of the brain and spinal cord, is not yet known, both genetic and environmental factors are known to be involved, medical researchers say.

Just one copy of the mutated gene from either parent affects a key enzyme that leads to lower levels of vitamin D.  The researchers looked for the gene variant in more than 3,000 families of unaffected parents with a child with MS, and found 35 parents who carried one copy of this variant along with one normal copy.  In every one of these 35 cases, their child with MS had inherited the mutated version of the gene, they said.

"All 35 children inheriting the variant is like flipping a coin 35 times and getting 35 heads, entailing odds of 32 billion to one against," said George Ebers, lead study author at Oxford University.

The research strengthened the case for vitamin D being one potential contributory cause of MS.

"Current opinion suggests that a combination of genetic predisposition, environmental factors such as exposure to sunlight and possibly some sort of trigger, such as a viral infection, interact in some way to start the development of MS," said Paul Comer of the charity MS Trust.

* * *

STUDY OF TWO SISTERS SHEDS LIGHT ON LYMPHOMA EVOLUTION

When a 41-year-old woman was diagnosed with CHRONIC-PHASE MYELOID LEUKEMIA, she received a bone marrow transplant and subsequent leukocyte infusion from her sister. These treatments controlled her leukemia, but seven years later, both sisters developed FOLLICULAR LYMPHOMA.

Although the phenomenon of a donor passing a malignancy to a recipient is well documented and considered a minimal risk to those in the transplant community, this case gave scientists the unique opportunity to understand the genetic abnormalities that led to follicular lymphoma in both cases.

“We were able to combine clinical activity with laboratory expertise to gain a real insight into the biology involved,” said David Weinstock, M.D., an assistant professor of medicine at Dana-Farber Cancer Institute, who published the case study in a recent issue of Cancer Discovery, the newest journal of the American Association for Cancer Research.  The study was funded by a Stand Up To Cancer Innovative Research Grant.

Both sisters are now in remission after standard CHEMOTHERAPY treatment. Weinstock’s research group will present their findings at the 2011 American Society of Hematology Annual Meeting and Exposition.

Weinstock and his colleagues sequenced the DNA of samples derived from the two sisters as well as a frozen sample of the leukocyte infusion to determine the genetic lesions that led to the lymphoma.  They found that both sisters had identical BCL2/IGH rearrangements and the same V(D)J rearrangement. They also identified 15 mutations that were present in both lymphomas. Researchers recovered 14 of these mutations from the donor lymphocyte infusions using ultra-deep sequencing — a finding that indicates that a lymphoma ancestor harboring these mutations was passed from the donor to the recipient seven years before clinical presentation.

Weinstock said this sort of knowledge could one day lead to an early treatment for follicular lymphoma.   “Currently the only curative approach is stem cell transplantation, but the more we understand about the genetic aberrations that lead to follicular lymphoma, the better we’ll be able to manage the disease,” said Weinstock.

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FDA, OTHER COUNTRIES REVIEWING APPLICATION FOR NEW RA DRUG

Drugmaker Pfizer Inc. says the Food and Drug Administration has accepted its application for approval of its experimental drug for adults with moderate to severe RHEUMATOID ARTHRITIS.  The FDA says it expects to rule by August 2012 on the application for tofacitinib, which Pfizer has touted as a promising new treatment for the autoimmune disease.

Tofacitinib is in a hot new class of pills for rheumatoid arthritis called JAK inhibitors, which block the janus kinase enzyme. The enzyme plays a key role in the inflammation process in which the immune system attacks joints, particularly in the hands and feet.

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The final piece is by Theresa Brown, an oncology nurse who's not only one helluva good writer, but belongs to that special stratum of healers who combine skill and compassion, with the strength necessary to face a daily onslaught of patients who are dealing with what's probably the most difficult time of their lives, physically.  Okay, I admit it, these people are my personal favorite heroes:

LOOKING FOR A PLACE TO DIE

By Theresa Brown

The patient was a fairly young woman and she'd had cancer for as long as her youngest child had been alive.  That child was now walking and talking and her mother's cancer had spread throughout her body to the point where there were no more curative options.  Aggressive growth of the disease in her brain had stripped her of her personality and her memories.

She had aother child, too, a few years older, and a husband whose drawn eyes and tense frame bore the strain of trying to keep it all together.  Extended family lived far away and couldn't be brought closer.  The husband and kids lived more than an hour's drive from the hospital.

No one could say for sure how long she would live, but continued hospital care was clearly pointless.  Nor could she go home: she needed more attention than her family could provide  Everyone -- her physician, the husband, the palliative care team, we nurses -- agreed she needed inpatient hospice care, and that it should be provided close to home.

The problem was, she had no place to go.  There was a hospice facility near her house, but it would accept her only if she would die within six days.

I've run up against these kinds of time limits before in my work as an oncology nurse.  There's a certain logic to it: hospice insurance benefits are ideally used to cover the costs of end-of-life care in patients' homes, for up to six months, while periods of inpatient care are for the "short term".  And although patients do die in inpatient hospices, part of the mission of hospice is allowing patients to remain at home instead of in a hospital; hence the turn away from inpatient care, which is costly and often intrusive.

But that leaves people like this patient -- more than a few days away from death, unable to be adequately cared for at home and unable to afford to pay out-of-pocket for a facility -- struggling to find a place to die.

Dying at home was neither safe nor compassionate for this patient.  She needed constant supervision: she would struggle to sit up and moan in frustration, or lurch dangerously over the side of the bed.  Her speech was more sounds than words, and she had no control over her bowels or bladder.

Her husband looked as if he might fold in on himself at any minute, and he's already borne the burden of care for a long time.  Though I didn't know for sure, it's likely that his insurance couldn't guarantee continuous nursing care in the home as a covered expense.  And the patient's children had already lost so much of their mother; she no longer even recognized them.  Did they need to sitness her final deterioration up close at home?

Home was not the only option.  She could have stayed in the hospital and pursued aggressive care.  Indeed, if her physician or a family member had said "do everything," meaning keep her alive as long as possible through intravenous medications and hydration and, ultimately, sending her to the intensive care unit on a ventilator, it would have cost thousands of dollars but, paradoxically, most insurance companies would have considered it a legitimate care option.

Doing everything possible to extend her life wouldn't have benefited her or her family, though.  Roughly a third of family members of I.C.U. patients show symptoms of post-traumatic stress, according to research by the French intensive-care expert Elie Azoulay and his collaborators.  If a loved one dies in intensive care after discussions about advance directives and patient wishes -- that is, after the family has been made fully aware of the finality of the situation -- the psychological fallout is even greater, approaching 80%.  We do not always aid the living by inflicting high-tech ministrations on the almost-dead.

In other words, inpatient hospice care made sense medically, financially and psychologically for this patient, but the system simply wouldn't allow it.

The only option, then, was for me to convince the hospice staff that she would die within six days.  I spoke with the inpatient coordinator, the administrator and the hospice admissions nurse, who came to the hospital floor to assess the patient.

My explanations were precise: "She's on an antibiotic now, but that'll stop in hospice so she could go septic  Her kidney function is already diminished; kidney failure is only a matter of time.  She has periods of difficulty breathing, and hospice won't have the respiratory support she'll need, but you can give her morphine to stop the air hunger."

All of us will at some point come to this pass; we will all need a place to die.  It's not easy to think about, but it is true.  We can turn away from that hard fact, try to stall death, even bend it to our will for a little while in the I.C.U.  Or we can face that most difficult of life's trials and ask ourselves how to make it easier.

With this patient I ended up being persuasive enough, and she got her inpatient admission.  Was she dead in six days  Probably; I don't know for sure  What I do know is that her sad husband and two young children, who would never really know their mother, had a chance to grieve and say goodbye in the most humane way possible for them.

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That's all, folks!   

But here's something to think about for the coming two months:  One aspect of the latest Congressional fiasco that didn't make the headlines, is the cut Medicare will make - an astounding 27% - to the payments they will make to doctors, if the more radical of our legislators have their way.  Even if no one we know needs those doctors' services, it's worthwhile to remember, and to remind our representatives (an oxymoron, if ever there was one) that these are the doctors who, like oncologists, face down death on a daily basis, keeping us and those we care about alive.  They should be getting a raise, instead of getting bitch-slapped by people who only care about the bottom line.  Tell the people in your state to stand up!  (Susan and Joanna, go get 'em!)