All posts by CPTFeditor

Free patient booklet on ductal carcinoma in situ (DCIS)

Breast Cancer, In the News, news-you-can-use, Uncategorized

To view, download, or print a free copy of our patient booklet, here is a PDF of DCIS: What You Need to Know.

The Cancer Prevention and Treatment Fund has developed a free, easy-to-read 32-page color booklet for women diagnosed with ductal carcinoma in situ (DCIS). It explains DCIS and commonly used medical terms in plain language and helps women make informed decisions about their treatment.

If a woman has a particularly low-risk type of DCIS, she may choose “active surveillance” instead of surgery and other treatment. Active surveillance consists of closely watching the patient’s DCIS to make sure it does not develop into breast cancer. The patient can choose surgery and other treatments if the DCIS develops into breast cancer, or if she decides she wants surgery for any other reason. Another option for women with particularly low-risk types of DCIS is to take the hormone pills tamoxifen to prevent breast cancer, rather than surgery.

Experts estimate that at least half of all women diagnosed with DCIS would never develop breast cancer even if they never received any treatment for their DCIS. Since no one knows for sure which women with DCIS will develop breast cancer and which won’t, most women with DCIS choose to get some form of surgery. This booklet focuses on helping women decide what kind of surgery to get and what other kinds of treatment they might want or need.  Patients should keep in mind that if their physician tells them that they have a particularly low-risk type of DCIS, they may want to consider active surveillance or tamoxifen only, rather than surgery in addition to other treatments.

The current booklet was approved and funded by a grant from the D.C. Cancer Consortium through the Department of Health, Government of the District of Columbia, and a grant from the Jacob and Hilda Blaustein Foundation.  To request copies of the free patient booklet, write  info@stopcancerfund.org   or call    202-223-4000.

We are currently updating the booklet to include information about active surveillance. 

AIDS activist takes up a new fight: defending FDA

In the News

This Associated Press article quotes Gregg Gonsalves’ testimony at the Senate briefing hosted by the National Center for Health Research on June 12, 2014.

By Matthew Perrone

WASHINGTON (AP) — As an AIDS activist in the early 1990s, Gregg Gonsalves traveled to Washington to challenge the Food and Drug Administration.

Photo from Associated Press. In this July 22, 2014 photo, AIDS activist Gregg Gonsalves walks outside Grand Central Terminal during a photo session, in New York. In the early 1990s, Gonsalves traveled to Washington to confront, provoke and challenge officials at the Food and Drug Administration. A quarter century later, he still travels to Washington, but with a very different agenda: to defend the FDA. (AP Photo/Richard Drew)
Photo from Associated Press.
In this July 22, 2014 photo, AIDS activist Gregg Gonsalves walks outside Grand Central Terminal during a photo session, in New York. In the early 1990s, Gonsalves traveled to Washington to confront, provoke and challenge officials at the Food and Drug Administration. A quarter century later, he still travels to Washington, but with a very different agenda: to defend the FDA. (AP Photo/Richard Drew)

Gonsalves was part of the confrontational group AIDS Coalition to Unleash Power, which staged protests outside the FDA’s headquarters, disrupted its public meetings and pressured its leaders into speeding up the approval of experimental drugs for patients dying of AIDS.

A quarter century later, Gonsalves still travels to Washington, but with a different agenda: to defend the FDA.

At a recent forum on FDA issues, Gonsalves implored congressional staffers to protect the agency from growing anti-regulatory sentiment that he worries will roll back safety and effectiveness standards for all types of drugs. The efforts include new state laws designed to undercut the FDA’s authority by giving patients early access to unapproved drugs and a lobbying push by industry groups to speed up the time it takes the FDA to review new treatments.

Both initiatives come at a time when researchers who study the FDA say the caricature of a slow, outdated bureaucracy is inaccurate. The FDA reviews most drugs in 10 months and high-priority drugs in six months or less. And a 2012 review in the New England Journal of Medicine showed that FDA regulators approve new drugs faster than their counterparts in Europe and Canada.

“The rhetoric we hear today is that FDA stifles innovation, that FDA keeps drugs out of patients’ hands. And you know, that was our rhetoric in 1989,” says 50-year-old Gonsalves, now a program director at Yale University. “But there’s no countervailing narrative that we need a strong FDA.”

The story of how Gonsalves went from FDA critic to supporter is intertwined with the AIDS movement’s impact — and its unintended consequences — on the agency.

Groups like ACT UP showed that FDA’s bureaucracy could be influenced by outside pressure. Following protests by ACT UP, the FDA went from taking over two years to approve most drugs to clearing HIV drugs in a few months. In the early 1990s, those shorter review times were written into laws that have governed FDA procedures ever since. But while the push for ever-faster reviews was kicked off by AIDS activists, it is now primarily driven by pharmaceutical lobbying groups and libertarian think tanks.

Since May, three states — Colorado, Louisiana and Missouri — have passed laws designed to allow terminally ill patients to receive experimental drugs that have not been cleared by the FDA. Arizona will vote on its own so-called “right to try” initiative in November and lawmakers in Florida, Oklahoma and Utah are set to introduce similar bills. All of these efforts are driven by lobbyists from the Goldwater Institute, a libertarian think tank.

Supporters have dubbed the measures “Dallas Buyers Club” laws, after the Oscar-winning movie about an AIDS patient who thwarts FDA regulators by smuggling in HIV drugs from overseas. And lawyers for the Goldwater Institute acknowledge that groups like ACT UP helped pave the way for their strategy, though they say more deregulation is needed.

“Many, many groups have been trying to get FDA reform for decades and the only real successful movement was the AIDS movement,” says Christina Sandefur, an attorney with the Arizona-based Goldwater Institute.

Mark Harrington, executive director of the Treatment Action Group, which spun off from ACT UP in the 1990s, says AIDS activists have long tried to distance themselves from such anti-Washington efforts. By the mid-1990s, Harrington and Gonsalves were actually pushing for longer, larger studies of HIV drugs. That’s because the first drugs approved by the FDA were linked to dangerous side effects, including anemia and nerve damage.

Harrington says the Goldwater-backed state laws are political theater that will not help desperate patients. “They’re providing false hope and really pushing quack cures and medicines that could be unsafe and ineffective,” he says.

Federal law makes clear that patients do not have a right to experimental drugs and the Supreme Court has refused to hear challenges to FDA’s authority over the matter. For its part, the FDA already gives dying patients access to unapproved medicines if drugmakers are willing to provide them.

“The agency stands ready to work with companies that are interested in providing access to experimental drugs,” said FDA spokesman Stephanie Yao, in a statement.

But there’s nothing in the state laws that require companies to grant early access.

While the FDA faces pushback from conservative activists at the state level, it is also faces industry pressure at the federal level.

House lawmakers have held half a dozen hearings this year on “accelerating the pace of cures in America.” The push is part of a pharmaceutical industry-backed initiative dubbed “21st Century Cures,” designed to streamline the drug approval process.

“There is no doubt that our antiquated, patch-work clinical trial system makes developing new treatments a cumbersome, expensive and protracted process,” said the Friends of Cancer Research group in recent congressional testimony. The group receives funding from Pfizer Inc., GlaxoSmithKline and many other drugmakers.

Some FDA watchers say it’s too early to worry about a major overhaul of the agency. Congress is gridlocked and no major health legislation is expected to pass until after the next presidential election.

But Gonsalves isn’t wasting time. In closing his talk on Capitol Hill earlier this summer, Gonsalves warned Senate staffers that a political shift to the right in coming elections could “change the game” for drug safety and effectiveness.

“We will have a different FDA than we have had for the last 30 years.”

Photo credit to the Associated Press, click here for the original story online.

Comments on proposed rule to allow FDA to regulate all tobacco products

Testimony & Briefings

Division of Dockets Management
Food and Drug Administration
5630 Fishers Lane, Room 1061 (HFA-305)
Rockville, Maryland 20852

August 8, 2014

Comments of members of the Patient, Consumer, and Public Health Coalition
On proposed Deeming Rule
Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Regulations on the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Products; Extension of Comment Period
Docket No. FDA-2014-N-0189

As members of the Patient, Consumer, and Public Health Coalition we are writing to comment on various aspects of the proposed rule to extend FDA’s jurisdiction to tobacco (including made or derived from tobacco) products other than cigarettes, including e-cigarettes. It is essential that the proposed rule be strengthened, since nicotine is highly addictive.

1.      We strongly oppose exempting any cigars from the rule, including those designated as “premium.”  According to the FDA’s deeming rule, “a large cigar may contain as much tobacco as a whole pack of cigarettes” and “nicotine levels in cigar smoke can be up to 8 times higher than levels in cigarette smoke.”  We concur with the FDA that “all cigars are harmful and potentially addictive,” and this is true regardless of their price, the size of the manufacturer, and whether or not they are handmade. In addition, providing cigars special treatment encourages cigarette and other tobacco-related product manufacturers to continue to misclassify products that are actually cigarettes as cigars, in order to take advantage of this regulatory loophole.

2.      We also strongly oppose exempting or weakening the rules for smaller manufacturers or manufacturer of “premium” tobacco products, regardless of their so-called “unique challenges.” As noted above, cigars can be more dangerous than cigarettes.  Regardless of the cost or whether they are manufactured on a small scale, cigars have large-scale, long-term health consequences.

3.      The FDA’s proposed rule does not go far enough to safeguard the health of young people. It proposes a national minimum age of 18 for the purchase of the newly deemed products, which we wholeheartedly endorse, but it permits sale through the internet where age verification is difficult if not impossible to enforce. For this reason, we urge the FDA to prohibit internet sales of the deemed products (and eventually all tobacco products), or  require sellers to adopt the same age verification procedures established under the 2009 Prevent All Cigarette Trafficking Act for internet sales of cigarettes and smokeless tobacco.

4.       The proposed rule does not go far enough to restrict the marketing and advertising of e-cigarettes and cigars to minors. The number of middle and high school students who reported ever using e-cigarettes doubled between 2011 and 2012; and high school boys are just as likely to smoke cigars as they are cigarettes (16.4% vs. 16.5%). E-cigarettes, cigars and other newly deemed tobacco products should be kept behind store counters just like cigarettes.  They should not be displayed in the open, like the candy that many of these newer tobacco products try to emulate, with flavors like “Cinnamon Apple Crunch,” “Tahitian Punch,” and “Iced Berry.

The proposed rule permits self-service displays, does not prohibit low-cost, mini packs of cigars (that are obviously more affordable to children) and also allows brand sponsorship of concerts or sporting events popular with teenagers. These should all be strictly prohibited. Moreover, the FDA has not proposed limiting the advertising of the deemed products the way cigarettes and smokeless tobacco advertising has been limited. By allowing unfettered advertisement of e-cigarettes and cigars, the FDA is ensuring that youth will continue to be exposed to ad campaigns as effective as the ones in years past, which equated cigarette use with glamour, sex appeal, and cartoon characters like Joe Camel.

5.      We strongly support the FDA’s proposal to include health warnings about nicotine addiction on all nicotine-containing tobacco products, including e-cigarettes and cigars. We also support the FDA proposal to require that all cigars, including premium cigars, carry additional rotating health warnings on the risk of mouth and throat cancer; the risk of lung cancer and heart disease; the risk of lung cancer and heart disease from secondhand smoke; and stating that cigars are not a safe alternative to cigarettes. However, we strongly urge the FDA to include a fifth warning on the increased risk of infertility, stillbirth and low birth weight. This is particularly important, given the growing popularity of cigars among teenagers and the fact that teenage girls and young women have the highest rates of smoking during pregnancy (16.6% for girls 15-19 and 18.6% for women 20-24 in 2005). We also urge the FDA to revert to the 12-month compliance period (from the date of the final rule) which was changed after OMB review to an unacceptably long 24 months.

According to the CDC’s June 2014 report, nearly one-quarter of all male high school seniors smoke cigars (23%). To save lives, the FDA should mandate its proposed warning about nicotine addiction for all tobacco products; require all cigar manufacturers to rotate all five of the warnings that the FTC imposed on seven cigar manufacturers in 2000; and stipulate that all warnings must be in effect no later than 12 months from the final rule.

6.      We also urge the FDA to strengthen the proposed rule regarding characterizing flavors in cigars or e-cigarettes.  Cigarettes, for instance, can only be sold with tobacco-flavor or menthol flavor; the newly deemed products should be held to the same standard as they are similarly addictive, nicotine-containing products. More than 80% of adult cigarette smokers began smoking before the age of 18; flavors like “bubble gum” and “banana split” are specifically designed to appeal to children and teens and attract people who otherwise would not use a tobacco product.

The bottom line regarding flavored nicotine products: any flavor that makes the use of tobacco products more palatable should be banned. If a major benefit of e-cigarettes is to cut back on regular cigarette use, then those buying e-cigarettes will not be seeking candy or fruit flavors.  These flavored options clearly promote the use of tobacco products by new customers.

7.      The proposed rule does not mention requiring child-resistant packaging of liquid nicotine for use in e-cigarettes. Given the alarming rise in nicotine poisonings resulting from children coming into contact with “e-juice,” FDA should issue a proposed rule to prevent this public health problem.

8.      The FDA is proposing a premarket review requirement for all newly deemed products, while recommending that manufacturers have 24 months from the final rule to file substantial equivalence and new product applications. This would allow manufacturers to keep existing products on the market and introduce new deemed products for two full years following the promulgation of the final rule. It would also allow products for which an application has been submitted to stay on the market unless or until FDA denies it. These loopholes are unacceptable, given that there has already been a 3-year delay in issuing the deeming rule, giving companies more than enough time to prepare for regulatory requirements. To reduce any further delay, the FDA  should: a) issue a final rule within a year of the proposed rule’s issuance, and no later than April 25, 2015, and b) shorten the period for submitting new application or proving substantial equivalence to one year from the final rule.

The Tobacco Control Act (TCA) was enacted in 2009 to give FDA the authority to prevent and control tobacco use. The deeming rule is meant to extend that authority so as to protect children and adults from the harms of cigars and e-cigarettes. We recommend further strengthening the deeming rule in the ways described above and/or concurrently issuing additional proposed rules. The FDA’s mission is to protect and advance public health, and unfortunately the proposed rule falls short.

American Medical Women’s Association
Annie Appleseed Project
Breast Cancer Action
Cancer Prevention and Treatment Fund
Connecticut Center for Patient Safety
National Alliance for Hispanic Health
National Consumers League
National Organization for Women
Our Bodies Ourselves
Women Advocating Reproductive Safety
WomenHeart

The Patient, Consumer, and Public Health Coalition can be reached through Paul Brown at (202) 223-4000 or at pb@center4research.org 

Johnson & Johnson praised for taking uterine surgery tools off market

In the News, News Stories & Editorials
By Katie Thomas, The New York Times
July 31, 2014

morcellator

Johnson & Johnson, which has come under withering criticism for its response to problems with some of its medical devices, won cautious praise from critics on Thursday for its decision to withdraw three products used in uterine surgery because of a risk of spreading cancerous tissue, only months after the safety issue became widely known.

Some experts continued to debate the medical value of the devices. A handful of other, smaller companies sell similar products.

The Ethicon unit of Johnson & Johnson said Wednesday that it was asking hospitals to return three types of power morcellators, devices that are commonly used in uterine surgery to remove fibroids by cutting the tissue into tiny pieces and extracting them through small incisions. In April, the Food and Drug Administration recommended that doctors stop using the procedure after the agency concluded that the risk of spreading cancer was higher than previously thought. That led Johnson & Johnson to announce that it would suspend sales and marketing of its products while it studied the issue, but it stopped short of withdrawing them from the market.

In a letter sent to health care providers, Ethicon asked that hospitals return three models of power morcellators made by the company: the Gynecare Morcellex and Gynecare X-Tract tissue morcellators, as well as the Morcellex Sigma tissue morcellator system.

About 50,000 operations a year involve power morcellation of tissue containing fibroid tumors, according to the F.D.A.

Some critics said they were pleasantly surprised that Johnson & Johnson acted as quickly as it did. “The company has had a rather abysmal track record on the public health front of ethical breaches in the last few years, so this is good that they’re doing this,” said Diana Zuckerman, president of the National Center for Health Research, a public health advocacy group that has criticized the company in the past over its safety record, especially concerning pelvic mesh implants. Dr. Zuckerman owns stock in Johnson & Johnson and her father, now retired, worked for many years in quality control at the company. Speaking of the decision on the power morcellators, she said, “At least it goes back to an earlier time when the company was seen as doing the right thing.”

The move comes as some in the gynecology field continue to disagree about the usefulness of power morcellators. Although the risk of spreading cancer through this procedure has been previously known, it was long believed that the chances for spreading cancer were lower, ranging from 1 in 10,000 to 1 in 500. In April, the F.D.A. concluded that the risk was closer to 1 in 350.

Still, some doctors cautioned against vilifying the procedure, saying that power morcellation allows minimally invasive surgery that, if carefully done, can be a better choice for some women. Without morcellation, more women will have to undergo serious abdominal surgery, which carries the risk of infection, bleeding, pain and blood clots. “These are things that people also die of,” said Dr. Barbara Goff, director of gynecological oncology at University of Washington. “So my concern is that we aren’t looking at this in balance.”

That medical debate is the reason Prof. Erik Gordon, who teaches business at the University of Michigan and has previously criticized the company for its safety record, said he was surprised that it acted as quickly as it did. “This is one of those things where it’s enough up in the air that you might have expected Johnson & Johnson to say, well, we’re going to keep it on the market because the evidence is inconclusive,” he said. “But that’s not what they did.”

Testimony of Dr. Anna E. Mazzucco, scientific advisor, on Ablatherm ultrasound treatment for prostate cancer

Testimony & Briefings
July 30, 2014

My name is Dr. Anna Mazzucco.  Thank you for the opportunity to speak today on behalf of the Cancer Prevention and Treatment Fund.   After completing my Ph.D. at Harvard Medical School, I conducted research at the National Cancer Institute.  Those are the perspectives I bring today.

Our research center conducts research, analyzes data in the research literature, and then explains the evidence of risks and benefits to policymakers and consumers.  Our president is on the Board of Directors of the Alliance for a Stronger FDA, which is a nonprofit dedicated to increasing the resources that the FDA needs to do its job.  Our organization does not accept funding from medical device companies, and therefore I have no conflicts of interest.

Prostate cancer is a very common cancer and all the current treatments have serious side effects that harm men’s quality of life.  The question today is whether the Ablatherm high-intensity focused ultrasound device is safe and effective for the treatment of low-risk, localized prostate cancer.  Most men diagnosed with localized, low-risk prostate cancer will not die from prostate cancer, but from something else.  Recent studies support active surveillance as a very reasonable option for these patients, since interventions do not improve overall survival and often harm quality-of-life.  The decision to treat low-risk early-stage prostate cancer, if at all, is already a challenging one for both patients and clinicians.  They deserve to be able to make important decisions which can affect quality-of-life for years to come based on solid scientific information.

For these reasons, any proposed treatment for this patient group must provide solid research evidence about the risks and benefits, so that patients and their families can make an informed decision.  I think we can agree that a new device, such as this ultrasound device, will not truly benefit patients unless it demonstrates a superior safety and quality-of-life profile.  Or, if you believe that options are good, at least the evidence should be solid that it provides an equally safe and effective result.

This is not the case with the Ablatherm ultrasound device.

First of all, we know almost nothing about its safety or effectiveness because the company has provided registry data on 62 patients, and of these, safety data were provided for more than 3 months for only 35 patients.  As the FDA noted in its executive summary, this is a very small number of patients to assess the safety of a treatment which could be used for thousands of patients.

In our opinion, the FDA should not even ask for your advice for a device studied on so few patients, given that other alternatives are available.

The lack of long-term safety data is especially important because on the average, a man diagnosed with prostate cancer will live at least 15 years before he will die of something other than prostate cancer.

Another methodological problem is that the patients whose safety was studied is not identical to the patients analyzed for effectiveness.  In fact, the two patient groups differ in several clinically meaningful ways, including age and concomitant therapy.  Patients and physicians need to be able to consider both the risks and benefits of any treatment together as it relates to their particular situation.

Despite these shortcomings, the sponsor attempted to make cross-study comparisons between this safety cohort and the radical prostatectomy arm of the PIVOT trial.  As the FDA scientists pointed out, unlike the Ablatherm data, the safety analysis from the PIVOT trial was not limited to a low-risk group, but included all risk groups, and the two trials also had completely different follow-up schedules.  These differences make any comparisons between these two groups completely meaningless.

The sponsor also attempted to perform a second safety analysis using the single arm of the incomplete Ablatherm IDE trial, again attempting to cross-compare to the PIVOT study.  This is also highly problematic for all the reasons stated by FDA scientists in their executive summary, including inability to compensate for differences in prognostic factors, follow-up schedules, and clinical endpoints.

As FDA scientists also noted, it could have been informative to compare the safety profile of Ablatherm to the active surveillance arm of the PIVOT trial, as that is a common approach to clinical management of this patient group.  But this was not done, and is impossible to do because of insufficient information.  Therefore, we are asked to judge the safety of this device with very little data indeed.

Despite these complications, several observations about the safety of the Ablatherm device can be made.

As you all know, quality-of life-is a particular problem for men treated for prostate cancer.  Two years after being treated with Ablatherm, 43.7% of patients still had erectile dysfunction and 11.1% still had incontinence.

There is no high-quality evidence of effectiveness either.  The only data are cross-study comparisons with the PIVOT study.  The primary efficacy endpoint was 8 year metastasis-free survival.  As the FDA scientists pointed out, due to the low event rate of metastasis in this low-risk patient group, and the high likelihood that these patients will not die of prostate cancer, this surrogate endpoint has little value.  Furthermore, attempting a cross-study comparison of a time-to-event endpoint, when the trials had different bone scan schedules, is again highly questionable.

The FDA scientists also highlight the fact that in the PIVOT trial being used here, radical prostatectomy was not superior to active surveillance in terms of metastasis  — or overall survival.

In other words, it makes no sense to try to prove that this new device is equal to surgical treatment regarding metastasized cancer when the surgical treatment is NO BETTER THAN NO TREATMENT.

The FDA scientists also point out similar methodological challenges comparing the Ablatherm data and registry and meta-analysis data from cryotherapy studies.

In summary, we simply do not have any properly controlled clinical data to support either the safety or effectiveness of the Ablatherm device.  Only 1 % of medical devices go through the PMA approval process.  The goal is to provide solid scientific evidence to prove safety and effectiveness so that patients and their physicians can make treatment decisions which can affect quality-of-life for years.   Registry data of only 62 patients, no minority patients, with no control group, and only 35 with safety data past 3 months is completely inadequate.  I can’t stress that enough.

We respectfully urge the committee to recommend that FDA reject this PMA application until better quality data are available.

 

Comment:

The FDA advisory panel voted against approval for the Ablatherm device, expressing concerns about lack of data on safety and effectiveness.

Click here to see our testimony slides.

 

 

The wrong approach to breast cancer

In the News, News Stories & Editorials
By Peggy Orenstein
New York Times
July 26, 2014

BERKELEY, Calif. — ONE of the nastier aspects of breast cancer is that it doesn’t have the five-year sell-by date of some other malignancies: you’re not considered “cured” until you die of something else. Although it becomes less likely, the disease can come back eight, 10, even 20 years after treatment. I fell on the wrong side of those odds.

I had a tiny, low-grade tumor in 1997; 15 years later, in the summer of 2012, while I was simultaneously watching “Breaking Bad,” chatting with my husband and changing into my pajamas, my finger grazed a hard knot beneath my lumpectomy scar. Just as before, time seemed to stop.

The recurrence appears to have been confined to my breast and was, like the original tumor, a slow-moving form of the disease. Since the lumpectomy and radiation I had in 1997 failed, however, this time the whole breast had to go. My first question to my oncologist (after “Am I going to die?” Answer: yes, someday, but probably not of this) was whether I should have the other breast removed, just to be safe.

It turns out, I’m not alone in that concern. After a decades-long trend toward less invasive surgery, patients’ interest in removing the unaffected breast through a procedure called contralateral prophylactic mastectomy (or C.P.M., as it’s known in the trade) is skyrocketing, and not just among women like me who have been through treatment before.

According to a study published in the Journal of Clinical Oncology in 2009, among those with ductal carcinoma in situ — a non-life-threatening, “stage 0” cancer — the rates of mastectomy with C.P.M. jumped 188 percent between 1998 and 2005. Among those with early-stage invasive disease, the rates went up 150 percent between 1998 and 2003. Most of these women did not carry a genetic mutation, like the actress Angelina Jolie, that predisposes them to the disease.

Researchers I’ve spoken with have called the spike an “epidemic” and “alarming,” driven by patients’ overestimation of their actual chances of contracting a second cancer. In a 2013 study conducted by the Dana-Farber Cancer Institute in Boston, for instance, women under 40 with no increased genetic risk and disease in one breast believed that within five years, 10 out of 100 of them would develop it in the other; the actual risk is about 2 to 4 percent.

Many of those same young women underestimated the potential complications and side effects of C.P.M. Breasts don’t just screw off, like jar lids: Infections can occur, implants can break through the skin or rupture, tissue relocated from elsewhere in the body can fail. Even if all goes well, a reconstructed breast has little sensation. Mine looks swell, and is a remarkably close match to its natural counterpart, but from the inside it feels pretty much like a glued-on tennis ball.

Of course, as any cancer patient will tell you, our fear is not simply of getting cancer, it’s of dying from it. What’s a mere mammary gland when, as Amy Robach, a journalist at ABC News, told People magazine last year after her own C.P.M., “I want to be at my daughters’ graduations. I want to be at their weddings. I want to hold my grandchildren.”

Unfortunately, for most women, C.P.M. is irrelevant to making those milestones. The most comprehensive study yet, published earlier this month in the Journal of the National Cancer Institute, showed virtually no survival benefit from the procedure — less than 1 percent over 20 years.

Researchers used the Surveillance, Epidemiology, and End Results registry and other databases to model survival chances for women who opted for C.P.M. and those who did not. They took into account a woman’s age at diagnosis, the stage and biology of her original tumor, the likelihood of dying from that cancer, the risk of developing cancer in the healthy breast, and the potential of dying from a new cancer. They even tweaked the numbers, nearly doubling the risk of contracting a second cancer and exaggerating the aggressiveness of a new tumor and the effectiveness of C.P.M.

“The story didn’t change,” Todd M. Tuttle, chief of surgical oncology at the University of Minnesota and the study’s senior author, told me. “Even if we used unrealistic figures, the conclusions were still the same. There was no group with a survival benefit of even 1 percent.”

How can that be? Well, first of all, it is extremely rare for a tumor on one side to spread to the other. Cancer doesn’t just leap from breast to breast. In any case, cancer confined to the breast is not deadly. The disease becomes lethal only if it metastasizes, spreading to the bones or other organs. Cutting off the healthy breast won’t prevent the original tumor from doing that. As for developing another cancer, Dr. Tuttle said, when that does happen (and remember, it’s far less common than patients believe), 91 percent will be early-stage lesions, so more readily treatable.

There’s some indication that patients understand that, yet choose C.P.M. anyway. The majority of the young women in the Dana-Farber survey knew the procedure wouldn’t prolong life; even so, they cited enhanced survival as the reason they had undergone it.

Such contradictions aren’t unusual, according to Steven J. Katz, a professor of medicine and health management and policy at the University of Michigan, who studies medical decision making. In exam rooms, all of us — men, women, cardiovascular patients, diabetics, cancer patients — tend to react from the gut rather than the head. “The general response to any diagnosis is, we want to flee it,” Dr. Katz explained. “It’s the kind of fast-flow decision making that we’re wired to perform. And it’s very difficult at that point to put data before a patient.”

I get that. When my cancer was first diagnosed, I felt as if a humongous cockroach had been dropped onto my chest. I could barely contain the urge to bat frantically at my breast screaming, “Get it off! Get it off!” Physicians, according to Dr. Katz, need to better understand how that visceral reaction affects treatment choices. They also need to recognize the power of “anticipated regret”: how people imagine they’d feel if their illness returned and they had not done “everything” to fight it when they’d had the chance. Patients will go to extremes to restore peace of mind, even undergoing surgery that, paradoxically, won’t change the medical basis for their fear.

Mothers inevitably cite their children as motivation for radical treatment; self-sacrifice has, after all, long defined good motherhood. It seems almost primal to offer up a healthy breast — with its connotations of maternal nurturance — to fate, as a symbol of our willingness to give all we have to and for our families. It’s hard to imagine, by contrast, that someone with a basal cell carcinoma on one ear would needlessly remove the other one “just in case” or for the sake of “symmetry.”

Treatment decisions are ultimately up to the individual. But physicians can frame options and educate patients in a way that incorporates psychology as well as statistics. Beyond that, doctors are not obliged to provide treatment that is not truly necessary.

The good news is that treatment to reduce the risk of metastasis has improved over the years. Not enough, but significantly. So those of us who dream of dancing at our children’s weddings? We may yet get there. But if — when — we do, it won’t be because of C.P.M.

Testimony of Dr. Anna Mazzucco on morcellation devices for uterine fibroid removal

Testimony & Briefings
Testimony of Dr. Anna E. Mazzucco
Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee
July 11, 2014

Thank you for the opportunity to speak today on behalf of the Cancer Prevention and Treatment Fund. My name is Dr. Anna Mazzucco, and after completing my Ph.D. in Cell and Developmental Biology from Harvard Medical School I conducted research at the National Cancer Institute. I speak from those perspectives today.

Our nonprofit organization conducts research, scrutinizes data in the research literature, and then explains the evidence of risks and benefits to patients and providers.  Our president is on the Board of Directors of the Alliance for a Stronger FDA, which is a nonprofit dedicated to increasing the resources that the FDA needs to do its job.  Our organization does not accept funding from medical device companies, and therefore I have no conflicts of interest.

About 600,000 hysterectomies are performed annually in the United States, according to the Centers for Disease Control and Prevention, and approximately 65,000 myomectomies.  Of the hystectomies alone, the FDA estimates that 50,000 to 150,000 use power morcellation.  The FDA also estimates that 1 in 350 women undergoing hysterectomy or myomectomy for the treatment of fibroids has unsuspected uterine sarcoma which could be spread and worsened if a power morcellator is used.  Based on these numbers, as many as 400 women could have undiagnosed malignancy spread each year from hystectomy alone  — when you add myomectomies, it is probably much higher.  We agree with the FDA that there is currently no reliable method to distinguish between uterine fibroids and sarcoma before surgery.  Training physicians is, unfortunately, not the answer.

The estimate of one in 350 women undergoing surgery having an unsuspected uterine cancer is based on recent studies and is much higher than the 1-in-10,000 chance of undiagnosed cancer typically quoted to patients.  The FDA has also estimated that undiagnosed cancer will be spread or worsened by morcellation in 25-65% of cases.  The estimated 5-year survival is 60% for patients with stage I disease, compared with 22% for those with stage III and 15% for those with stage IV.

Minimally invasive surgery can offer many advantages to patients, but as you have heard at this meeting, the mortality benefits of such procedures are unclear. In contrast, it is absolutely certain that malignancy spread by morcellation can be life-threatening.  In light of these findings, we agree with the FDA’s statement in their safety communication that power morcellators should no longer be used during removal of uterine fibroids. 

The question is whether this warning from the FDA is enough to save lives?  Or, is this new evidence sufficient to alter the classification and labeling of these devices?

Power morcellators were originally approved as class II moderate -risk devices under the 510(k) process, which does not require clinical trials prior to allowing the device on the market.  It also does not require inspections to make sure the device is made and working as designed — such inspections are required for all prescription drugs.  Since morecellators were not studied in clinical trials, the risk of undiagnosed sarcoma spreading was not detected prior to clearance through the 510(K) pathway.  As a result, patients were irreparably harmed.  We’ve heard some of those tragic stories at this meeting.

Class III devices are defined as those which pose a significant risk of illness or injury, and require clinical testing for safety and efficacy.  Clearly, power morcellators meet this definition and should be classified as Class III devices.  Therefore, they should undergo clinical studies before any more patients are harmed.  Non-clinical performance testing studies are simply not sufficient to address these safety concerns.   If an adequate number of patients had been studied in clinical trials, we would have known years ago that morcellators could cause a fatal spread of uterine cancer.

I think everyone on this panel agrees that more research is needed. Clinical studies must evaluate risk mitigation strategies, such as use of a companion containment bag. However, as the FDA briefing material cites, there are adverse events associated with current specimen bags.  For this reason, bags need to be specifically designed for use with power morcellators specifically for uterine fibroids.  Surgical techniques must also be refined for use with these bags.

Clinical trials are also needed to improve the accuracy of patients’ diagnostic outcomes when morcellators are used.

After these studies are completed, the FDA should consider whether and under what circumstances power morcellators can be used for uterine fibroids.   On the basis of research, black box warnings must inform physicians and patients of the risk of spreading malignancy and the required risk mitigation strategies.  This label should also include the warning that these devices should never be used in patients with suspected malignancy.  Training and certification should also be required before physicians can use power morcellators to ensure that these risk mitigation techniques have been mastered.

As the FDA has stated in its summary for today’s meeting, the current voluntary reporting system for medical devices is underused, and thus underreports adverse events for all medical devices, including power morcellators. Unfortunately, surgeons and other medical personnel are not reporting these incidents to the FDA, and their reporting is voluntary, so they don’t have to.  On the other hand, the hospitals where these incidents occur are required to report them to the device companies, and the device companies are required to report them to the FDA.  For some reason, those reports were not being made either.  As a result, many more patients died before the risks of morcellation became known — primarily as the result of a physician whose life was put at risk when a morcellator used for a uterine fibroid resulted in Stage 4 uterine cancer.

We agree with the American Congress of Obstetricians and Gynecologists that a patient registry should be created to follow patients whose fibroids were previously removed with the assistance of power morcellation to more scientifically monitor their health outcomes. But, that is not enough.  And the current FDA warnings are not enough.

We need higher standards to ensure that morcellation devices are safe and effective, and that require clinical trials with sufficient numbers of patients to determine the risks of rare but fatal outcomes.

Cancer Prevention and Treatment Fund joins more than 3 dozen groups in supporting bills that ban hormone chemicals from food and beverage cans

In the News, Legislation, Policy

Read the text of the letter, signed by dozens of health and cancer related organizations, below:

July 9, 2014

The Honorable Lois Capps

2231 Rayburn House Office Building

Washington, DC 20515

The Honorable Grace Meng

1317 Longworth House Office Building

Washington, DC 20515

Dear Representative Capps and Representative Meng,

The undersigned organizations are pleased to express support for the Ban Poisonous Additives Act of 2014 (S. 2572/H.R. 5033). By banning bisphenol A (BPA) in food packaging and requiring the FDA to review the safety of other chemicals in food packaging, your legislation is an essential step toward improving the health of all Americans.

Most people are exposed to BPA every day. According to the U.S Centers for Disease Control and Prevention, more than 93 percent of the public have detectable levels of BPA in their bodies. Although the presence of BPA in commonly used goods is shockingly prevalent, the average consumer is unaware of its potential danger or what products to avoid.

BPA is the building block for polycarbonate plastic and used in the epoxy resin linings of food cans. More than 300 independent human and laboratory studies have found evidence that BPA exposure at very low doses is linked to a staggering number of health problems, including breast and prostate cancer, obesity, attention deficit and hyperactivity disorder, altered development of the brain and immune system, lowered sperm counts and early-onset puberty.

BPA raises a particular concern for vulnerable populations such as women of childbearing age and young children. Even minuscule amounts – as small as a few parts per billion or parts per trillion – have been shown to cross the placenta and disrupt normal prenatal development. In addition, workers exposed to BPA in the process of making and packing food cans are also at risk.

Twelve states have already adopted legislation to ban BPA from baby bottles and sippy cups, and 3 of those states also banned BPA from infant formula and baby food. Following the lead of these states and a long list of retailers and manufacturers that banned BPA in food containers for young children, including CVS, Gerber, Kroger, Safeway and Toys R Us, the FDA ended its authorization of BPA in baby bottles and sippy cups in July, 2012. A year later, in response to a petition from then Rep. Markey, the FDA also banned the use of BPA in infant formula packaging.

Banning BPA in the packaging of young children’s food is critical; however, to fully protect children from exposure to BPA and other chemicals of concern, we need to protect pregnant women and all of the foods that pregnant women and young children may ingest. Your legislation would also for the first time include workers as a vulnerable population that must be considered when the FDA reviews the safety of the chemicals in food packaging.

Americans expect and believe that our government is safeguarding their health and the health of their families from dangerous chemical exposures, and your legislation is an important step in that direction. We applaud your leadership on this issue and look forward to working with you to protect the public health by banning BPA from all food and beverage containers and requiring the FDA to ensure the safety of other food contact substances.

Sincerely,

Alaska Community Action on Toxics

Alliance of Nurses for Healthy Environments

American Congress of Obstetricians and Gynecologists

American Nurses Association

Black Women for Wellness

Breast Cancer Action

Breast Cancer Fund

Cancer Prevention and Treatment Fund

Center for Effective Government

Center for Environmental Health

Center for Food Safety

Clean and Healthy New York

Clean Water Action

Coalition for a Safe and Healthy CT

Conservation Minnesota

Consumers Union

Ecology Center

Empire State Consumer Project

Environmental Health Strategy Center

Environmental Working Group

Greenpeace

Health Care Without Harm

Healthy Child Healthy World

Healthy Legacy Coalition

Huntington Breast Cancer Action Coalition

League of Conservation Voters

Learning Disabilities Association of America

MomsRising

Mossville Environmental Action Now

National WIC Association

Physicians for Social Responsibility

SafeMinds

Safer Chemicals, Healthy Families

San Francisco Bay Area Physicians for Social Responsibility

Science and Environmental Health Network

TEDX, The Endocrine Disruption Exchange

WE ACT for Environmental Justice

Women’s Voices for the Earth

 

Testimony of Dr. Anna E. Mazzucco to FDA advisory committee on olaparib

Testimony & Briefings, Uncategorized
June 25, 2014

Thank you for the opportunity to speak today on behalf of the Cancer Prevention and Treatment Fund. My name is Dr. Anna Mazzucco, and after completing my Ph.D. in Cell and Developmental Biology from Harvard Medical School I conducted research at the National Cancer Institute. I speak from those perspectives today.

Our nonprofit organization conducts research, scrutinizes data in the research literature, and then explains the evidence of risks and benefits to patients and providers.  Our president is on the Board of Directors of the Alliance for a Stronger FDA, which is a nonprofit dedicated to increasing the resources that the FDA needs to do its job.  Our organization does not accept funding from pharmaceutical companies, and therefore I have no conflicts of interest.

Maintenance therapy for ovarian cancer patients is vital to extending the recovery time between chemotherapeutic regimens and preserving the efficacy of those agents.  Under consideration today is whether there is sufficient evidence at this time to approve olaparib for a maintenance therapy indication for platinum-sensitive high-grade relapsed serous ovarian cancer.

The goal of maintenance therapy is to extend the time between therapeutic intervals with an optimal risk-benefit ratio.  Otherwise, these patients would not be taking any medication during this time and need this period to recover before additional chemotherapy is needed.  Therefore safety, efficacy, and quality-of-life measures are defining features of maintenance therapy.

Afterreviewing the study evidence, we have three major concerns about olaparib, which were also raised by the FDA.

Firstly, we are concerned about the reliability of the progression-free survival benefit of olaparib, especially since there was no improvement in overall survival during Study 19.

Secondly, we are concerned about the safety profile of olaparib in the context of maintenance therapy. Olaparib-treated patients were almost twice as likely to experience a serious adverse event, in addition to the potentially elevated occurrence of myelodysplastic syndrome orAML.

Lastly, we are concerned that there is not enough evidence of efficacy and low toxicity to ensure that use of olaparib will not compromise patient response to subsequent therapy, which is critical to successful maintenance therapy.

Previous studies of first-line therapy for ovarian cancer suggested that progression-free survival can be predictive of overall survival.  However, a recent paper by the Society of Gynecologic Oncology cautioned against extrapolation of progression-free survival to presumed overall survival benefit in the context of prolonged post-progression survival and multiple lines of treatment.

I’m sure we all agree with the FDA that overall survival is clearly the most significant efficacy measure.  Progression-free survival may only be an acceptable efficacy endpoint when certain criteria are met.  These criteria include low toxicity and efficacy which is both truly predictive of clinically significant benefit and is of robust magnitude, in this particular case, an extension of progression-free survival by six months or more.

Given these stipulations, the seven month extension of progression-free survival in gBRCAm patients may meet a minimal efficacy threshold, but there are strong concerns about the reliability of this observed effect.  In the exploratory analysis conducted by the FDA within the placebo arm, the gBRCAwt/vus population unexpectedly had a superior progression-free survival outcome when compared to the gBRCAm population.  This suggests that the placebo-treated gBRCAm population may have “underperformed”, meaning that the progression-free survival improvement observed in the gBRCAm population may be overestimated.  The SOLO-2 trial currently underway is powered to precisely detect changes in the hazard ratio.  That data is critical to clarifying the potential progression-free survival benefit of olaparib due to this uncertainty.

While the patient-reported FACT-O quality-of-life measures did not indicate detriment, there were significantly increased adverse events with olaparib treatment, including a 2-fold increase in nausea, a 4-fold increase in anemia, a 2-fold increased incidence of various infections, and a near 2-fold increase in gastrointestinal disorders.

As the FDA stated, the patient-reported measures may not capture all possible negative effects of olaparib treatment, and any reported improvements could also reflect cessation of previous platinum treatments.

In addition, approximately four times as many patients in the olaparib-treated arm versus the placebo-treated arm underwent dose reductions, and about six times as many underwent dose interruptions due to adverse events.  Many adverse events also lasted longer in the olaparib-treated arm. There were ten adverse event categories which lasted more than a month longer for olaparib-treated patients, including abdominal, joint, musculoskeletal pain and nausea.  For these reasons, we are concerned that olaparib does not meet the low toxicity and quality-of-life parameters that are essential in the maintenance therapy setting.

The ongoing phase III SOLO-2 trial has the potential to clarify the potential progression-free survival benefit of olaparib, in addition to providing an additional analysis of overall survival and quality-of-life measures.

The results of SOLO-2 are needed In order to be able to guarantee patients an effective maintenance therapy that is not likely to jeopardize their quality-of-life and overall prognosis.  Therefore, we urge the committee to delay approval of olaparib until sufficient evidence has been provided.

Members of the Patient, Consumer, and Public Health Coalition strongly support the Research for All Act of 2014

Legislation, Policy

To view as a PDF, click here.

June 5, 2014

The Honorable Jim Cooper
1536 Longworth HOB
Washington, DC 20515

Re: Members of the Patient, Consumer, and Public Health Coalition strongly support the Research for All Act of 2014.

Dear Congressman Cooper,

As members of the Patient, Consumer, and Public Health Coalition, we strongly support the Research for All Act.  It would require the FDA to develop policies to ensure that clinical trials for medical products granted expedited approval are sufficient in design and size to determine the safety and effectiveness for men and women, using subgroup analysis.  The Act also increases the study of female animals, tissues, and cells in basic research conducted or supported by NIH.

This legislation is needed because most medical research used as the basis of FDA approval decisions focuses on men. For example, although cardiovascular disease is the leading killer of women and men, only one-third of subjects in clinical trials are female.  Even when studies do include women, 70% fail to report outcomes by sex.  Insufficient inclusion in clinical trials, failure to conduct appropriate subgroup analysis, and lack of publically available information puts women at risk when they use FDA-approved diagnostics and treatments.  As an example, the unique way women metabolize drugs was not considered when the dosage for Ambien sleeping pills was determined.  As a result, the recommended dosage was approximately twice as high for women as it should have been.  It took many years before the FDA finally corrected the label to reflect different dosages for men and women.

Expedited pathways are designed to make important new drugs readily available; it is essential that the companies utilizing these pathways ensure that their products are safe and effective for women as well as men.

Men will also benefit by requiring clinical trials to report outcomes by sex. Low-dose aspirin has different preventive effects in women and men; there is now evidence that a diabetes drug may lower a women’s risk of heart failure but increase men’s risk; and some common blood pressure and antibiotic medications may be less effective for men.  These potential problems are not identified if men and women are analyzed together rather than separately.

Thank you for sponsoring this legislation. The Research for All Act will improve health outcomes for women and men by more precisely ensuring the proper indication and dosage.

 

American Medical Student Association
American Medical Women’s Association
Annie Appleseed Project
Breast Cancer Action
Connecticut Center for Patient Safety
Consumers United for Evidence-based Healthcare (CUE)
Jacobs Institute of Women’s Health
National Center for Health Research
National Physicians Alliance
National Women’s Health Network
Our Bodies Ourselves
Ovarian Cancer Alliance of San Diego
The TMJ Association
Center for Science and Democracy at the Union of Concerned Scientists
WoodyMatters
WomenHeart

 

The Patient, Consumer, and Public Health Coalition can be reached through Paul Brown at (202) 223-4000 or pb@center4research.org