Category Archives: Other Cancers

Testimony of Dr. Diana Zuckerman About PEPAXTO FDA Advisory Committee Meeting on September 22, 2022

I’m Dr. Diana Zuckerman, president of the National Center for Health Research. We scrutinize the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products.  Our largest program is focused on cancer.  My expertise is based on post-doc training in epidemiology and public health, and previous positions at HHS and faculty member and researcher at Yale and Harvard.

All of us want more treatment options for refractory cancers, but we want patients to be able to have confidence that FDA approval means a product is proven safe and effective.  The OCEAN study of 495 multiple myeloma patients has important information that was not available when the drug received accelerated approval. Even if some patients taking Pepaxto do well, it is only with a randomized controlled trial that we can determine if Pepaxto is helpful or if the patients would do better without it.

Our Center’s analyses support the FDA findings that the data do not confirm the indication.  In the randomized trial comparing Pepaxto to another treatment option, median survival was 5.3 months shorter, and the death rate was slightly higher. 

The Sponsor says some patients do better but we agree with FDA that “Results from subgroup analyses cannot be used to conclude benefit in a subset of patients, when the overall patient population has shown a detrimental treatment effect.”

We also agree with the FDA that PFS is not improved and that “An anti-cancer therapy that prolongs PFS is not considered safe and effective if the therapy results in a detrimental effect on OS”

Public trust in the FDA has been weakened in recent years.  FDA standards matter to all of us.  Would you want your loved one to take Pepaxto rather than a superior treatment option?  Not all oncologists will be as knowledgeable about the data as those serving on this panel.

It concerns us that the sponsor continues to ignore FDA concerns, rely on shortcuts instead of better research, and that the company withdrew the drug in October but then rescinded the withdrawal.  Was this just a delaying tactic?  We agree with the FDA that the sponsor did not provide new data, and with Dr. Pazdur that FDA approval relies on solid information about appropriate dosage, which is lacking here.

Maybe Pepaxto would benefit some types of patients and better research is needed to prove that.  As FDA states, the preponderance of evidence from the prespecified analysis and in all other subgroups suggests an increased risk of death in patients and a potential for harm.”

We were pleased that the Committee voted 14-2 that the evidence does not support that the benefits outweigh the risks.

Why Are Celebrities Removing Their Breast Implants?

Amelia Murphy, Cancer Prevention & Treatment Fund

Every now and then, a new celebrity is in the news after announcing her decision to remove her breast implants. They speak out about the importance of loving yourself the way you are, they post some Instagram pictures of “the new me,” and the public eagerly reads the related articles in tabloid magazines.

But most of these women aren’t just talking about body image; they are getting their implants removed because of their health. Breast implants can make some women so sick that removal is their best hope for feeling like themselves again.  Several celebrities are trying to spread this information to the general public.

Crystal Hefner, Hugh Hefner’s wife, opened up about her breast implant horror story on Facebook. She announced her implants had been slowly poisoning her and causing unexplained back pain, cognitive problems, constant neck and shoulder pain, recurring infections, and many other symptoms. Once she removed her breast implants, she instantly felt an improvement and continues to feel better. [Read more about her story in this Forbes article]

Yolanda Foster, of Real Housewives fame, removed her breast implants when she found out her silicone implants had ruptured and were leaking into her body. The silicone was making the symptoms of her Lyme disease even worse. She felt much better once she removed her implants.

Linda Blair, actress in the horror movie The Exorcist, described her experience with breast implants as a nightmare. After removing her implants, she advocated for the FDA to make sure breast implants are actually studied to be safe.

Mary McDonough, a child star in The Waltons who appeared as an adult in shows such as ER and Will and Grace, attributes her autoimmune disease (lupus) to her breast implants. She was healthy before getting implants, and it was only after her implants were removed that she immediately started to feel better. She has been one of the most outspoken celebrities on the risks of breast implants.

Karen McDougal is a former Playboy Playmate and current model who made the decision to have her implants removed after months of feeling sick. She has spoken out about the risks of breast implants in USA Today and People Magazine.

Mariel HemingwaySharon Osbourne, and Stevie Nicks are just a few of the other celebrities who chose to remove their breast implants because of serious health problems.

Celebrities are bringing attention to the health problems that thousands of women with implants have suffered from for decades.

First, a little history:

Women have been getting breast implants since the 1960’s, and although silicone gel implants were drastically restricted for many years during the mid-1990’s through 2005 because of safety concerns, the FDA approved them again in 2006 based on short-term studies done by breast implant manufacturers. FDA also required the manufacturers to do larger, longer-term studies after that, in order to make sure they were safe (these are called post-market studies).

These longer-term studies had a lot of problems, and most women did not stay in the studies long enough to provide useful scientific information.  However, studies have shown that the longer women have silicone breast implants, the more likely they are to experience problems with them.  FDA reported that the studies found that as many as 1 out of every 5 women who get silicone breast implants for cosmetic reasons need to remove their implants within 10 years.[1] This number rises to 1 out of every 2 women if they got reconstruction after a mastectomy.[1]  Were the women who dropped out of the studies the ones that were more likely to have health problems, or less likely?  You can read more about the unanswered questions from these studies here.

Breast implants were approved by the FDA even though research showed that between 15% and 20% of first-time augmentation patients will need additional surgery to fix implant problems within 3 years, whether the implants are filled with silicone gel or saline. [2][3] The chances of needing additional surgery increases as time goes on — 28% of women are on the second set of implants after 3 years, and this number doubles when the women have their implants for 6 years. The percentage is even higher than that for mastectomy patients whose implants were for reconstruction.

What usually goes wrong?

  • Rupture: All breast implants will eventually break, sometimes within a few months or years, and usually within 10 years.
  • Capsular Contracture: This is when the breasts get firm, then hard, and they can be very painful. Breast implants are a “foreign body” and the natural response for most women is that their body forms scar tissue around the implant, inside their body, to protect their body from this “foreign invader.”  This is a natural process. However, it’s called capsular contracture when the scar tissue tightens or hardens around the implants and causes abnormal firmness, hardness, or pain.
  • Pain: Besides pain caused from capsular contracture (see above), breast implants can cause back, neck, and shoulder pain because of their weight. Leaking silicone gel can also cause a painful burning sensation.
  • Autoimmune issues:  Experts disagree on whether breast implants cause specific autoimmune diseases.  However, the fact that implants can cause cancer of the immune system (ALCL) certainly makes it more likely that implants can cause other autoimmune problems.  FDA scientists found that women with ruptured and leaking silicone gel breast implants were more likely to have fibromyalgia, a painful autoimmune disease.[5]  Many women have reported suffering from autoimmune symptoms such as joint pain, hair loss, dry eyes, or mental confusion after getting breast implants, and have also reported that these symptoms often improve or disappear after removing the implants. One study even showed the autoimmune symptoms got better for 3 out of 4 women after they removed their implants.[6]
  • Constant flu-like symptoms: Many women report feeling constantly tired or like they’re trying to get over the flu.
  • Learn more about complications from breast implants in FDA’s consumer handbook.

Besides health problems, some celebrities decide to remove their implants simply because they were annoying or embarrassing. Just to name a few, Heather MorrisHeidi MontagPamela AndersonVictoria Beckhamand Jane Fonda all removed their implants for this reason.

Plastic surgeons refer to breast augmentation as a very simple surgical procedure, and as a result many people think of breast implants as an insignificant surgery with few health risks.  Hearing about celebrities who removed their breast implants sometimes makes women think twice about getting them in the first place.  It helps remind all of us to do careful research before making any decision about putting something inside your body.


ALCL Update: In March 2017, the U.S. Food and Drug Administration (FA) updated its website to report that breast implants could cause a type of cancer of the immune system called Anaplastic Large Cell Lymphoma (ALCL). [4]  No celebrities have reported ALCL from their breast implants. .


Are you considering breast implants? Find out more information here.

Are you thinking about removing your breast implants? Find out more information here.

ALCL and Breast Implants: 2017 Update

Anna E. Mazzucco, PhD and Diana Zuckerman, PhD, Cancer Prevention & Treatment Fund

In March, 2017, the U.S. Food and Drug Administration (FDA) updated its website to officially report that breast implants could cause a type of cancer of the immune system called anaplastic large cell lymphoma (ALCL).  They stated they have received 359 reports of ALCL among women with breast implants.

The FDA’s announcement came 10 months after the disease was named breast implant associated ALCL (BIA-ALCL) in a  World Health Organization publication in 2016, and a few months after the and the National Comprehensive Cancer Network (NCCN) released the first worldwide oncology standard for the disease.  NCCN includes a guided algorithm for surgeons and oncologists to test for and diagnose the disease.  They concluded that any abnormal accumulation of fluid or a mass that develops near the breasts months after breast implants were implanted must be evaluated.

The oncologists also state that even if the BIA-ALCL is confined to the scar capsule that surrounds the implant and even if that capsule is totally removed through proper explant surgery, the patient must be followed for 2 years.  Here is the link to their guidelines:

Although rare, it seems that BIA-ALCL is not “very rare.”  In Australia, which can track medical problems from any kind of implants better than the tracking of implants in the U.S., they estimate that BIA-ALCL affects one woman per 1,000 with breast implants.  The estimates were much lower in the U.S., but there is no reason to think BIA-ALCL is less likely to develop in women in the U.S.  Given the dramatic increase in diagnoses in recent years, it is clear that BIA-ALCL was under-diagnosed and under-reported for many years.

The sooner ALCL is diagnosed, the more likely it can be treated easily and effectively by removing the implants and capsule.  At later stages, treatment includes chemo and is less likely to be successful, as specified by researchers at the well-respected MD Anderson Cancer Center in a medical journal in 2013. Their study followed women for 5 years and found that ALCL related to breast implants sometimes requires chemotherapy, and approximately 25% of the implant patients with the more serious type of ALCL died during the 5 years following their diagnosis.[1] Dr. Anna Mazzucco published a response to this study,[2] urging physicians to respond quickly and to check patients who have swelling near their implants for ALCL. This would require cytology testing rather than testing for bacteria. The authors of the original study also published a response to Dr. Mazzucco’s article, expressing similar concerns.[3]

For more information, see our summary of that study here.

ALCL caused by breast implants can result in swelling, which is often mistaken for an infection and treated with antibiotics. Antibiotics are ineffective against ALCL and the delay in timely and appropriate treatment for ALCL is dangerous.

Unfortunately, some health insurance companies have traditionally not covered the cost of medical tests or treatment for women with breast problems related to cosmetic breast implants. The published articles on ALCL clearly indicate that this can result in undetected cancer of the immune system (ALCL), which can be fatal. In addition, delays in treatment for ALCL can be extremely expensive for patients and their insurance companies; the companies would be required to pay for treatment for ALCL when it is eventually diagnosed at a later stage.


  1. Miranda RN, Aladily TN, Prince HM, et al: Breast implant–associated anaplastic large-cell lymphoma: Long-term follow-up of 60 patients. J Clin Oncol 32:114-120, 2014.
  2. Mazzucco, AE. Next Steps for Breast Implant-Associated Anaplastic Large-Cell Lymphoma. J Clin Oncol, 2014.
  3. Miranda RN. Reply to AE Mazzucco. J Clin Oncol, 2014. Early Release publication. June 16, 2014.

Good news for coffee drinkers: the health benefits outweigh the risks for most people

By Morgan Wharton, Jessica Cote, and Shahmir Ali

latte-249102_640Most Americans drink coffee every day.1 The caffeine in coffee helps us stay alert but also may cause jitteriness and interfere with sleeping. A few studies suggest that decaffeinated coffee also has health benefits, perhaps because of antioxidants or acids in the coffee bean.2

What Are The Health Benefits Of Drinking Coffee?

For years medical experts advised people to drink less coffee, mostly because of research suggesting coffee might increase the risk of heart disease. However, numerous studies conducted recently have discovered coffee’s unexpected health benefits. Like all well-designed research, most of these studies considered the impact of age, sex, body mass index (BMI), physical activity, tobacco use, and whether family members had developed cancer. By controlling for those factors, researchers made sure they could separate coffee’s impact on health from the effects of people’s lifestyle, family history, and previous health problems. However, the type of coffee you drink may influence its health benefits; a very large study from the UK published in 2022 found that adults who drank larger quantities of unsweetened or sugar-sweetened coffee were less likely to die from cancer in the subsequent 7 years, and also less likely to die from any cause during that time frame.3  However, drinking more artificially sweetened coffee had no impact on cancer or other deaths.

Colorectal Cancer

Meta-analyses are a kind of statistics that combine data from several comparable studies to make one very large study. These results are usually more accurate than any one study can be. Taken together, three meta-analyses suggest that drinking about four or more cups of coffee per day may reduce the chances of getting colorectal cancer by 11-24%.456

Endometrial (uterine) Cancer

Using data from 67,470 women who participated in the Nurses’ Health Study, researchers found that women who drank four or more cups of coffee per day were 25% less likely to develop endometrial cancer than women who drank only one cup of coffee per day. Compared to women who did not drink any coffee, those who drank four cups or more per day were 30% less likely to develop endometrial cancer. Decaffeinated coffee was just as effective as caffeinated coffee, but caffeinated tea did not lower the risk of endometrial cancer.7

Liver Cancer And Cirrhosis (Scarring of the Liver/Chronic Liver Disease)

One study found people who drank one or two cups of coffee per day had a slightly lower risk of getting the most common type of liver cancer compared to non-drinkers, but people who drank three or four cups of coffee were about half as likely as non-drinkers to get this kind of liver cancer. Meanwhile, people who drank five or more cups per day had an even lower risk than that (about one-third the risk of non-drinkers).8

Similarly, a study in Japan found a 76% decrease in the risk of that type of liver cancer in people who drank at least five cups of coffee per day compared to those who did not drink coffee. The strongest benefit was seen in individuals with hepatitis C, a disease which increases a person’s risk of developing liver cancer, although the researchers were not sure why.9

A study of 120,000 Americans over an 8-year period found a 22% decrease in the chances of developing cirrhosis for each daily cup of coffee. In Norway, a 17-year study of 51,000 citizens found that those who drank two or more cups of coffee per day were 40% less likely to develop cirrhosis compared to those who did not consume coffee.10

Skin Cancer

Using data from two enormous studies, the Nurses’ Health Study and the Health Professionals Follow-up Study, researchers found that men and women who drank more than three cups of caffeinated coffee per month were 17% less likely to develop basal cell carcinoma compared to people who drank less than one cup per month. Basal cell carcinoma is the most common and least dangerous type of skin cancer. Drinking decaffeinated coffee did not affect basal cell carcinoma.11

A 2014 study in the Journal of the National Cancer Institute found that the more coffee participants drank, the less likely they were to develop malignant melanoma over a 10 year period. Melanoma is the most dangerous form of skin cancer. Almost 450,000 whites, aged 50-71, participated in the study. Researchers found that drinking four or more cups of coffee per day was linked to a 20% lower risk of getting malignant melanoma. Once again, drinkers of decaffeinated coffee lost out. Their risk of getting melanoma was no different from that of non-coffee drinkers. Coffee drinking, however, did not affect the least dangerous form of melanoma, called melanoma in situ.

Remember that no matter how much coffee with caffeine you drink, the best way to prevent skin cancer is still to limit your time exposed to the sun and ultraviolet light! 12

Type 2 Diabetes

People in Finland consume more coffee than almost any other nation, and a study of 14,000 people over 12 years  found that men who drank 10 or more cups of coffee daily had a 55% lower risk of developing type 2 diabetes than men who drank 2 cups of coffee a day or fewer.  Even more dramatic, women who drank 10 or more cups per day had a 79% lower risk of developing type 2 diabetes than those who drank fewer than 2 cups daily.13

A different Finnish study of 5,000 sets of identical twins found that individuals who drank more than seven cups of coffee per day had a 35% lower risk of type 2 diabetes than their twins who drank two cups or fewer per day.14 Because identical twins are so biologically similar, the difference in disease risk is very likely caused by coffee consumption levels. Studies of fewer people in other countries have found less dramatic but similarly positive results.

Parkinson’s Disease

A study of more than 8,000 Japanese-American men found that men who did not drink coffee at all were three to five times more likely to develop Parkinson’s disease within 30 years than men who drank four and a half cups or more of coffee per day.15


Because suicide may be related to alcohol intake, medications, and stress levels, suicide studies took those factors into account.  A 10-year study of 128,000 people in California found that the risk of suicide decreased by 13% for every additional cup of coffee consumed per day. Even one cup of coffee per day seemed to reduce the risk of suicide. A different 10-year study of 86,000 women found a 50% lower risk of suicide for those who drank two or more cups of coffee per day compared to women who did not drink coffee.16

Brain Power and Aging

A study of 676 healthy men born between 1900 and 1920 suggested that coffee helped with information processing and slowed the cognitive decline typical of aging. Cognitive functioning was measured by the Mini-Mental State Examination, a 30 point scale. Men who regularly consumed coffee experienced an average decline of 1.2 points over 10 years, while men who did not drink coffee saw a decline of 2.6 points over 10 years. Men who drank three cups of coffee per day declined only 0.6 points over 10 years.17

Even old mice are sharper with caffeine: a study using a mouse model of Alzheimer’s disease showed that coffee actually reversed the cognitive decline and slow-down in processing that occurred with age. Mice given caffeine in their water showed signs of recovering their memory during testing.18

What about the risks?


Two separate studies found that 300 mg of caffeine (two to three cups of coffee) decreased a woman’s chances of getting pregnant by more than a third. This same amount of coffee also increased the chances of women having low birth-weight babies by 50%. These studies took into account potentially influential  factors such as contraception used in the past and infertility history.19

Hip Fracture

According to data from the Nurses’ Health Study, women aged 65 and over who drank more than four cups of coffee per day had almost 3 times as many hip fractures over the next six years as women who did not drink coffee. Researchers took important factors into consideration such as how much calcium the women consumed each day.20

Parkinson’s Disease among post-menopausal women taking estrogen-only hormone therapy

Other researchers used data from the Nurses’ Health Study to evaluate the risk of Parkinson’s disease among women who drank coffee while using estrogen medication after menopause. For women who were NOT using estrogen therapy, those who drank four or more cups of coffee per day were about half as likely to develop Parkinson’s disease as women who did not drink coffee. For women who did use post-menopausal estrogen, however, those who drank four or more cups of coffee were about twice as likely as those who didn’t drink coffee to develop Parkinson’s.21

Heart Disease

Two different meta-analyses found that people who drank five or more cups of coffee per day were 40-60% more likely to develop heart disease compared to those who did not drink coffee at all. Other studies have also shown that high coffee use (five to ten cups per day) increases the risk of heart disease, while moderate consumption (three to four cups daily) was not associated with a higher risk. Only coffee drinkers who consumed more than nine cups a day had a greater risk of dying from heart disease.22 It is important to consider that people drinking close to 10 cups of coffee a day are likely to have other health problems, such as stress or sleep deprivation, and this could contribute to higher risk of heart disease and death regardless of coffee use.

Bottom line

For most people, drinking coffee seems to improve health more than harm it. Many of coffee’s health benefits increase with the number of cups per day, but even one cup a day lowers the risk of several diseases. However, women who want to get pregnant or already are pregnant and women over 65 should probably limit their coffee intake because, in their case, the risks may outweigh the health benefits.

Even though many studies show coffee has benefits, it’s still not clear why. How can one popular beverage help metabolism (for example, lowering the risk of type 2 diabetes) and also protect against a range of cancers? Until further research can solve that puzzle, most adults should continue to enjoy their cup (or two, or three) of Joe. Finally, remember that nearly all studies on coffee and health have been done on adults. Coffee may affect children and teens differently.

Gene Therapy May Provide Hope for Patients with Advanced Leukemia

Margaret Dayhoff-Brannigan, Cancer Prevention and Treatment Fund

Acute Lymphoblastic Leukemia (ALL) is difficult to treat in children and adults. The most effective treatment is a stem cell transplant, but for patients whose cancer comes back after stem cell treatments, or who cannot be treated with a stem cell transplant, there are very few other options.

A study published in the prestigious New England Journal of Medicine in October 2014 tested a new treatment on terminally ill patients, 78% of whom survived at least 6 months.23

What is Acute Lymphoblastic Leukemia?

ALL is a cancer of the blood and bone marrow. It is the most common form of leukemia in children. In a healthy person, blood consists of red blood cells which carry oxygen and nutrients, platelets that help wounds to heal, and white blood cells which help the body fight infection. These different types of cells are made from stems cells in the bone marrow. In a patient with ALL, there are too many abnormal white blood cells that do not work properly to fight infections. These patients do not have enough red blood cells and platelets, and that can cause anemia or excessive bleeding. 24

Treatment Options

Currently there are four treatment options for ALL patients. Chemotherapy is a common cancer treatment that uses drugs to kill cancer cells. Radiation therapy is a treatment for cancer that uses x-rays or other forms of radiation to kill cancer cells. Targeted therapy uses very specific drugs or substances to identify and attack only cancer cells without causing harm to normal cells. Chemotherapy with stem cell transplant combines chemotherapy (and sometimes radiation) to kill cancer causing stem cells in the body, and then replaces them with a donors stem cells.2 How successful the treatment is usually depends on how old the person is when they are diagnosed and the amount of white blood cells the person has. ALL has a cure rate of 80-90% in childhood cases, but only about 40% in adults. Approximately 1,170 adults and 270 children die of ALL each year.25

Two Promising New Treatment for Patients with Relapsed ALL

There are two promising new treatments, but more research is needed before doctors will know more about which patients are most likely to benefit and before these treatments will be widely available.

Researchers at two hospitals in Philadelphia used an experimental treatment for ALL on 25 children and 5 adults.1 The children were seen at Children’s Hospital of Philadelphia by Dr. Shannon Maude and Dr. Stephan Grupp and their colleagues. The adult patients were treated at the University of Pennsylvania School of Medicine under the care of Dr. Noelle Frey. These patients all had relapsed several times or had failed to respond to any treatment. All had only a few weeks or months to live. The scientists took blood from each patient and separated out the white blood cells. These cancerous white blood cells were then genetically modified so that they could recognize and attack the diseased cells that cause the leukemia. The genetically modified cells were then put back in the patient using a blood transfusion.

One month after the treatment, 27 of the 30 patients were in remission. However, as the study continued, 7 of the 27 had a relapse, anywhere from 6 weeks to 8.5 months after treatment. More relapses are expected as the study continues.

Overall, 78% of the patients in the study were still alive 6 months after treatment, which was much longer than would have been expected without the gene therapy.1 When the results were written up for publication, one patient had survived two years after therapy. However, approximately half the patients had received the treatment less than 7 months earlier (some as little as 1-2 months earlier), making it impossible to calculate the average number of months of survival for the 30 patients.

Although patients were selected for the study if they were not eligible for stem cell transplant, several became eligible after gene therapy improved their health, and successfully underwent stem cell transplants or another treatment. However, the patient who has survived for two years did so without additional treatment.

We expect that a subsequent publication will give 2-year follow-up data for all 30 patients.

A different and also successful treatment for patients with relapsed or untreatable ALL was published recently by a different group of scientists at the Memorial Sloan-Kettering Cancer Center in New York City. They used a similar method to modify the genes in the patients’ white blood cells. However, this treatment was only effective at giving patients a short period of remission while they were waiting for a stem cell transplant. None of the patients in this study could be cured without also receiving a stem cell transplant.26 In contrast, the treatment studied by doctors in Philadelphia is the first to offer the possibility of a long reprieve or even possibly a cure in patients who had very little time left to live.


A Special Focus on Carcinoid Tumors

Anna E. Mazzucco, Ph.D., Cancer Prevention and Treatment Fund

Although textbooks call them rare, the incidence of carcinoid tumors is on the rise.  In 1973, carcinoid tumors were diagnosed in only 8.5 people per million; by 1994 this number more than quadrupled to 38.4 per million.27 This increase could be due to several factors, such as more sensitive detection, increased awareness, and the larger number of Americans over the age of 50.28   However, the cause of the increase is unclear, and these tumors can be life-threatening.  When they grow and spread, these tumors often affect organs that show no symptoms until late in the disease. Like almost all cancers, earlier diagnosis is very important for the overall prognosis.

Carcinoid tumors belong to a larger medical category called neuroendocrine tumors, which are named for their “neural” (i.e. information-sensing) and “endocrine” (i.e. hormone-related) functions.  Carcinoid tumors are a particular type of neuroendocrine tumor, named to reflect being “carcinoma-like” or “carcinoid” due to their microscopic similarities to more aggressive cancers.  They are considered distinct types of tumors because they are usually very slow-growing.29  Instead of being named for the organ in which they occur, the unifying feature of carcinoid tumors is that they start in a particular kind of neuroendocrine cell, which can be found in several different organs.  That is why carcinoid tumors can be found in the stomach, appendix, colon, lung, and other organs, and also why the symptoms, treatment and prognosis of carcinoid tumors can also vary so much between patients.  The location and size of the tumor determine a lot about its characteristics and also which treatments are best.

Risk Factors

Scientists and physicians are still working to understand carcinoid tumors.  We know that there are a few traits which can increase a person’s risk of having a carcinoid tumor.  These include:

  • Age (50 and older)
  • Gender (female)
  • Family history of multiple endocrine neoplasia type I (MEN1)
  • Conditions which cause low stomach acid production, such as Zollinger-Ellison syndrome, pernicious anemia, and atrophic gastritis
  • Smoking (for atypical lung carcinoid tumors)


As carcinoid tumors can form in many different organs, symptoms vary by location, and can be similar to those of other health issues.  However, if you experience any of these symptoms for several days, call your doctor.

For carcinoid tumors of the gastrointestinal system, symptoms may include:

  • diarrhea or constipation
  • nausea
  • abdominal or rectal pain
  • rectal bleeding

For carcinoid tumors of the lungs, symptoms may include:

  • chest pain
  • wheezing or shortness of breath
  • skin discloration that looks like stretch marks
  • unexplained weight gain in the midsection or upper back

Another feature of carcinoid tumors which makes them different from other tumors is that they can cause symptoms which at first may seem unrelated to each other.  In these rare cases (only about five percent of all carcinoid tumor cases), the tumor can cause unusually high amounts of hormones in the blood.30  This situation, called carcinoid syndrome, could result in symptoms such as:

  • flushing
  • heart palpitations
  • large changes in blood pressure
  • swelling of legs and feet


Diagnosis may rely on several sources of information, such blood and urine tests, imaging tests such as CT or MRI, endoscopy, or biopsy.  Endoscopy allows closer visual examination of the tumor with a tiny camera passed through the digestive tract.  During an endoscopy, a biopsy sample may be collected, which is very small amount of tissue removed for analysis.  Based on this information, physicians will often classify carcinoid tumors as either typical or atypical.  They will also define a tumor as having “local”, “regional spread”, or “distant spread”, based on how far a tumor may have grown beyond its original location.


Surgery is often used as the first treatment for carcinoid tumors.  If the tumor hasn’t spread, surgery can cure the cancer.  Surgery may also be combined with other treatments to reduce the tumor and the symptoms.  If the tumor has spread to the liver, which is quite common, it can be surgically treated by blocking the artery to the liver with chemotherapy or injected polymer beads. Liver tumors can also be treated by radiofrequency (radiowaves) or cryotherapy (using cold to destroy cancer cells).2

The drugs most commonly used to treat carcinoid tumors are hormone therapies called somatostatin analogues, such as octreotide (Sandostatin) and lanreotide (Somatuline Depot), which are given as daily or monthly injections, respectively.  These drugs work to block the growth of the tumor and the hormones it may produce, and can be effective for long periods of time, although the dose may need to be increased over time.  Newer versions of these drugs, such as pasireotide, are being developed and compared to the older drugs to determine which are more effective, and for whom.   Other treatments are being developed that use these same drugs to deliver radiation directly to cancer cells, such as in MIBG therapy.   A different drug also used to treat carcinoid tumors is interferon (Intron A, Pegasys), which uses the body’s own immune defenses against the tumor.2  New studies are evaluating the safety and effectiveness of combining hormone therapies such as octreotide with interferon to see if they work better together.  Radiation and traditional chemotherapies are not usually helpful for slow-growing carcinoid tumors.  However, some carcinoid tumors (often called “atypical”) with higher growth rates (or high “proliferation index”) may respond to them.  Studies of combinations of chemotherapy drugs are being conducted to find out which are most effective.

As scientists are learning more about carcinoid tumors, new drugs called “targeted therapies” are being developed, which are based on a detailed biological understanding of the tumor.  Clinical trials are being done to investigate these new drugs for carcinoid tumors, such as everolimus (Afinitor), sunitinib (Sutent), azaspirane (Atiprimod), IGF-R1 blockers (AMG 479), and VEGFR and Akt inhibitors (such as Tricirinine, Axitinib, Votrient, Avastin, Cometriq, Ziv-aflibercept) 2,31  Everolimus and sunitinib have been approved by the Food and Drug Administration for the treatment of advanced pancreatic neuroendocrine tumors, but FDA will not approve these drugs for carcinoid tumors until clinical trials are completed to show whether they are safe and effective for those tumors.   Studies have shown that carcinoid tumors produce high amounts of particular proteins related to cell growth, including IGF-R1 and VEGFR2, and new drugs are being developed to block these molecules.32   Another new treatment, YF476, is being tested specifically for stomach carcinoid tumors.

If you are undergoing treatment for a carcinoid tumors, up-to-date information about clinical trials can be found here.   A healthy diet, exercise, and emotional support can also be helpful during treatment for cancer.  If you have questions about your treatment or want to know more about your treatment options, ask your doctor lots of questions and consider seeking another opinion until you receive the information you need.

Testimony of Dr. Jennifer Yttri at FDA Advisory Committee on Tivozanib

May 2013

I am Dr. Jennifer Yttri and I am speaking on behalf of the Cancer Prevention and Treatment Fund of the National Research Center for Women & Families. Our non-profit research center scrutinizes medical data, evaluating scientific evidence of benefits and risks for patients.  We analyze and review research and provide objective and understandable health information to patients, health care providers, and policy makers.  Our organization does not accept funding from pharmaceutical companies and therefore I have no conflict of interest.

Today’s fundamental question is whether the one completed Phase 3 clinical trial is enough to approve the new drug tivozanib as a treatment for patients with renal cell carcinoma.

FDA guidelines recommend two trials that support efficacy of a drug. In some cases, FDA will approve a new drug based on only one trial if that trial shows a significant improvement over existing therapy. In the FDA’s own words: “A conclusion based on two persuasive studies will always be more secure than a conclusion based on a single, comparably persuasive study. Reliance on only a single study will generally be limited to situations in which a trial has demonstrated a clinically meaningful effect on mortality, irreversible morbidity… and [when] confirmation of the result in a second trial would be practically or ethically impossible.”

The NDA submitted for tivozanib relies on one phase 3 study comparing tivozanib to sorafenib. While tivozanib was shown to increase progression free survival by 3 months in patients with renal cell carcinoma, it did not improve overall survival. In fact, there was a non-significant lower overall survival for tivozanib, suggesting the drug may actually harm patients more than it helps them. This one study alone is not enough to meet the FDA’s guidelines for drug approval.

In addition, the study results have inconsistencies that raise red flags about the research and about the drug itself.

1.       Patients receiving tivozanib had increased progression free survival, so why were they more likely to die in the first 30 days due to disease progression, compared to sorafenib. This does not make sense. The deaths in the first 30 days could be due to chance, but the disease free survival could also be due to chance.  More research is needed to clarify the risks as well as the long-term benefits.

2.       FDA noted that 70% of sorafenib patients stopped taking the drug at least temporarily and 44% ended up with a reduced dose. This is much higher than other studies – for example one study highlighted by the FDA had only 14% interruption and 10% reduction.  There is no logical explanation for this, but these unusual problems could make sorafenib seem inferior to tivozanib, when in fact it might be superior.

These inconsistencies may be due to chance or to irregularities in how the studies were conducted in other countries.  Standard of care and assessment of disease varies in the US and other countries, and fewer than 10% of patients enrolled in the trial were in the US.  We agree with the FDA reviewer that it is preferable to enroll US patients, so that the study reflects the disease burden and treatment in the US and can provide better insight into treatment outcomes for US patients.

Regardless of the reason for the inconsistencies in the study, a second, independent, phase 3 study would help determine the safety and efficacy of this drug for treatment of renal cancer.

We urge you to recommend that the FDA require the sponsor to complete a second trial to confirm the positive effect of tivozanib on PFS; address the concern over lower OS; and provide better information on how generalizable the results are in the US population. Based on the data provided, there are no ethical concerns with requiring another trial. With the additional information, the FDA can make an informed decision as to whether tivozanib meets their standards of safety and efficacy.  That is not possible based on this one study with such inconsistent results.

Is Newer and More Expensive Care Better?

Sarah Miller, RN and Laura Covarrubias

Is more medical care really better? What about all these new, expensive drugs and high-tech surgeries? Do they save lives or improve health?

If you answered yes to these questions, you are not alone, but you may not be correct. A study done by the American Institutes for Research on insured adults between ages 18 and 64, found that most thought that more care, newer medical technology, and more expensive care were better. In addition, the adults interviewed believed that all care met minimum quality standards, and they were skeptical of evidence-based medical guidelines.

A typical response was “I don’t see how extra care could be harmful to your health. Care would only benefit you.” Although this belief is widely held, it is not accurate.  For example, if a healthy 80-year old man or woman without cancer symptoms is screened for various types of cancer, any abnormal findings are likely to result in treatment that is unlikely to benefit them.  That is why the U.S. Preventive Services Task Force usually recommends against screening 80-year olds for these cancers, although they recommend diagnostic testing for patients of all ages if they have symptoms.

“You get what you pay for” is another popular opinion, with many people assuming that more expensive care is superior. However, care that is far less expensive is sometimes just as good or even better.  One example of this is robotic prostatectomy, a surgery for men with prostate cancer that is done by a robot operated by the surgeon. Many men want this type of surgery, which costs $2,600 more than a regular prostate surgery. Some studies have shown that men who have the robotic surgery have lower rates of complications after the surgery, but others have shown that there is no difference. Most researchers who have conducted studies on this agree that the robotic surgery has not yet been proven to be any better than regular prostate surgery.

Even if robotic surgery isn’t worse than the regular surgery, is it worth the extra $2600? Consider this: for every two insured men that choose to have regular rather than robotic surgery, the cost savings could more than pay for one uninsured man with prostate cancer to have this life-saving surgery.[5] This is important to consider in the United States, where many people are not able to afford their medical care.

A similar idea that many patients have is “if it’s newer, it’s better.” While it may seem like new treatments would be chosen because they are better, this is rarely true. For example, cetuximab (also called Erbitux) was introduced in 2008 as a new addition to treatment for lung cancer patients. Although the drug was called a breakthrough in treatment for lung cancer, the average patient taking the drug lived only 1.2 months longer than patients not taking the drug. And in the many months of taking the drug, 85% of patients experienced skin toxicity, which often caused great discomfort (Fojo & Grady).  And despite the small possible advantages of the drug, it cost $80,000 for just a few months of treatment, resulting in huge medical bills that many families could not afford.  Avastin for Stage 4 breast cancer is an even more dramatic example.  Avastin is used for many cancers, but after several years, it became clear that on average, the breast cancer patients taking it were not living any longer and were more likely to have a stroke or other very serious and debilitating reaction to the drug that could make their last months much more painful physically and psychologically.

Cereal companies regularly add “New” in big letters on cereal boxes, because that sells more products (even if what is new might be a new toy inside).  Patients should be more cautious.  While some patients may want to take the chance that a new drug might be better, but many would rather know what the risks are before trying a new medication that could be worse than the tried and true treatments.

Evidence-Based Guidelines

Medical guidelines are usually established by a group that is considered expert in the subject of the guidelines. Medical guidelines are usually based on evidence from scientific research and are written according to the agreement a group of experts comes to about what the research tells them is the best for patients.

Unfortunately, research indicates that many adults are skeptical about guidelines.  Many seemed to think that asking providers to use guidelines did not allow them to make decisions based on their own expertise and that they could be used to ration care so that people did not “take” too much. One participant said that medical guidelines are “taking your choice away and putting it in someone else’s hands.”

Contrary to the mistaken belief that providers were restricted to actions dictated by the guidelines, in reality, guidelines are meant to guide providers by making suggestions based on the best evidence. Providers are still able to make the final recommendation to patients based on their professional expertise.

Is a doctor’s individual experience more valuable than guidelines?  That’s hard to say, but usually it would not be.  Guidelines are based on evidence from medical research comparing large groups of people who have had different types of treatment. Therefore, guidelines based on science will, on average, provide the best care for most people.  However, a physician with impressive expertise may be able to predict which patients are more likely to benefit from other types of treatment.

For example, for years, it was recommended that women between 40 and 69 years of age have a mammogram every year to screen for breast cancer. In 2007, however, the American College of Physicians changed their guidelines to leave it up to physicians to decide whether women between 40-50 needed annual mammograms.  In 2009, the US. Preventive Services Task Force wrote new guidelines, based on research evidence from thousands of women. The new guidelines recommended that women age 40-49 should not have regular mammograms to screen for breast cancer unless they had an especially high risk of breast cancer, and that women age 50-75 should have screening mammograms every two years – extending the age to older women but cutting the frequency from annually to every other year.

Many people challenged the new guidelines believing they could substantially delay the detection of cancer, especially for women under 50.  Isn’t it always better to have a chance to detect cancer earlier?

The answer is yes and no. Although mammograms save the lives of many women (including those in their 40’s), they also expose women to harmful radiation that can actually cause cancer over the course of women’s lifetimes. The researchers considered other forms of harm as well, such as the emotional trauma of a “false positive” results that result in stressful and expensive biopsies.  They concluded that the potential for harm outweighed the potential benefits of mammograms for the average women under age 50 and over 75, as did annual rather than biyearly mammograms for women age 50-75.

Many people did not agree with the U.S. Preventive Services Task Force’s interpretation of the evidence, however.  It is partly a matter of interpretation.  The U.S. Preventive Services Task Force was advising average women, and some cancer advocates believe that it is too difficult to predict whether a person is at high risk or not.  As a result, groups such as the American Cancer Society prefer to err on the side of over-treatment and radiation exposures, rather than on the side of potential under-treatment and reducing radiation exposure.

Health care providers are able to judge the two sets of guidelines and decide what to recommend for specific patients. For example, a woman in her 30’s who has many family members with breast cancer, including some at a young age, may be advised to have digital mammograms every other year in their 30’s (because they are more accurate than traditional mammograms and use less radiation) and annually after that.

“All care meets minimum quality standards” is another common belief.  Most could imagine providers making an occasional mistake, but few thought that there were any providers who consistently delivered a quality of care that did not meet basic standards.[1] Unfortunately, research shows that health care varies from doctor to doctor, and many do not meet minimum quality standards. The quality of care that doctors provide varies by the type of clinic where they work (publicly or privately funded, for instance), the communication skills of the doctor, and even how much sleep the doctor has been getting (Manusukhani; Kenny; Philipson).

What Can We Learn From This?

This study gives some insight into why we spend so much on health care and why efforts to improve medical care are often opposed as “rationing” or “death panels.” Unfortunately, most patients want the newest and most expensive care, and don’t understand that it may not be as safe or as effective as older, less expensive treatments.

In the United States, we spend more per person on health care than any other country, and yet our citizens are not as healthy as those in Japan, France, and Cuba, countries that spend far less per person on health care.

In addition to wasting money on treatments that are no better, and are sometimes inferior, our wasteful spending also means that we have less money for other essential services, such as education, housing, and national security.4

Of course, there is a lot of very expensive medical care that is medically necessary and could save a person’s life, such as trauma care in an emergency room for someone who has been in a serious car accident. But, there are also popular treatments that are expensive and not necessary, like a woman having labor induced for convenience when it would be safer and less expensive to have a natural birth. The key is to eliminate the unnecessary care so that we can continue to afford the necessary, beneficial care.

When it is not clear whether more expensive care actually helps or is just a waste of money, medical research can point us in the right direction. That’s why it is a good strategy to require “comparative effectiveness research” to determine whether, for example, robotic prostate surgery is better than regular surgery, or just needlessly more expensive.  It is often not obvious which treatments are the best, and sometimes they are the most expensive treatments but other times they may be the least expensive treatments or no treatment at all.

Doctors and patients can be part of improving medical care, by asking whether research conclusively shows which treatment is safer and which is most effective, instead of wrongly assuming that guidelines are aimed at saving money, not improving care.


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  2. Centers for disease control and prevention. Births: Final data for 2006, National Vital Statistics Reports.
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