FDA Approves Cetuximab for Late-Stage Head and Neck Cancer

Source: The Oncology Report

The Food and Drug Administration on Nov. 7 approved cetuximab as an initial treatment of late-stage head and neck cancer in combination with chemotherapy.

Cetuximab, marketed as Erbitux by Bristol-Myers Squibb, is an epidermal growth factor receptor (EGFR) antagonist, administered as an intravenous infusion. Previously, it was approved in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma. It was also approved for use alone in patients with recurrent locoregional disease or metastatic disease whose disease has progressed following platinum-based chemotherapy.

The newly approved indication is for the treatment of these recurrent or metastatic patients as an initial therapy in combination with platinum-based therapy with 5-fluorouracil (5-FU), a BMS spokesperson said. (At press time, the company had not yet issued a statement on the approval.)

Erbitux was initially approved in 2004 to treat EGFR-positive late-stage colon cancer after patients stopped responding to chemotherapy and was approved in 2006 for the treatment of head and neck cancer. The newly approved indication is for “recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU,” according to the revised label, posted on the FDA Web site.

The two previously approved indications for head and neck cancer were for “locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy,” and for “recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.

“Erbitux’s ability to extend the lives of patients with head and neck cancers is an important tool for oncologists who often rely on a multitreatment approach for patients,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in the statement. “Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have as many treatment options available as possible,” he added.

The approval was based on a multicenter study of 442 patients who had metastatic or recurrent head and neck cancer, which was inoperable or widespread, and of those who had not been treated with chemotherapy. The study was conducted outside of the United States and used a version of cetuximab that is not approved in the United States, the statement said.

The median overall survival among patients who were treated with cetuximab and chemotherapy (cisplatin or carboplatin and 5-fluorouracil) combination was 10.1 months, compared with 7.4 months among those who received chemotherapy alone cisplatin or carboplatin and 5-fluorouracil, the FDA statement said.

The most common adverse events reported by patients in the cetuximab plus chemotherapy arm were rash; pruritus; nail changes; headache; diarrhea; and respiratory, skin, and mouth infections, according to the FDA.

Other adverse effects that have been associated with cetuximab include low serum levels of magnesium, potassium, and calcium; and potentially fatal infusion reactions and myocardial infarctions. Sun exposure should be limited during treatment.

Cetuximab available in the United States provides about 22% greater exposure than the European Union–approved cetuximab that was used in this study, but this pharmacokinetic data along with the results of this study “and other clinical trial data establish the efficacy of Erbitux at the recommended dose,” according to the revised prescribing information posted on the FDA Web site.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

2011-11-09T11:05:16-07:00November, 2011|Oral Cancer News|

Monitoring Tobacco-Specific N-Nitrosamines and Nicotine in Novel Marlboro and Camel Smokeless Tobacco Products: Findings From Round 1 of the New Product Watch

Source: OxfordJournals.org


Introduction: Information on chemical composition of the new oral “spitless” smokeless tobacco products is scarce, and it is not clear whether there is some variability as a function of purchase place or time due to either unintended or intended manufacturing variations or other conditions.

Methods: We analyzed tobacco-specific N-nitrosamines (TSNA) and nicotine in Marlboro Snus, Camel Snus, and dissolvable Camel products Orbs, Sticks, and Strips that were purchased in various regions of the country during the summer of 2010.

Results: A total of 117 samples were received from different states representing six regions of the country. Levels of unprotonated nicotine in Marlboro Snus and Camel Snus varied significantly by regions, with the differences between the highest and the lowest average regional levels being relatively small in Marlboro Snus (∼1.3-fold) and large in Camel Snus (∼3-fold). Some regional variations in TSNA levels were also observed. Overall, Camel Snus had significantly higher TSNA levels than Marlboro Snus, and Camel Strips had the lowest TSNA levels among all novel products analyzed here. The amount of unprotonated nicotine in the dissolvable Camel products was comparable to the levels found in Marlboro Snus.

Conclusions: Our study demonstrates some regional variations in the levels of nicotine and TSNA in Marlboro and Camel novel smokeless tobacco products. Continued monitoring of this category of products is needed as the existing products are being test marketed and modified, and new products are being introduced. This information is particularly important given its relevance to Food and Drug Administration regulation of tobacco products.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Kentucky Cancer Center Urges Smokers to Switch to Smoke-Free Tobacco. But is it Really a Better Option?

Source: Yourlife.USAtoday.com

In the smoker-heavy state of Kentucky, a cancer center is suggesting something that most health experts won’t and the tobacco industry can’t: If you really want to quit, switch to smoke-free tobacco.

The James Graham Brown Cancer Center and the University of Louisville are aiming their “Switch and Quit” campaign at the city of Owensboro. It uses print, radio, billboard and other advertising to urge smokers to swap their cigarettes for smokeless tobacco and other products that do not deliver nicotine by smoke.

Supporters say smokers who switch are more likely to give up cigarettes than those who use other methods such as nicotine patches, and that smokeless tobacco carries less risk of disease than cigarettes do.

“We need something that works better than what we have,” said Dr. Donald Miller, an oncologist and director of the James Graham Brown Cancer Center, which supports the effort along with the University of Louisville. “This is as reasonable a scientific hypothesis as anybody has come up with and it needs to be tried.”

The campaign runs counter to the prevailing opinion of the public health community, which holds that there is no safe way to use tobacco. Federal researchers, however, have begun to at least consider the idea that smokers might be better off going smokeless.

The National Cancer Institute at the National Institutes of Health says on its website that the use of all tobacco products “should be strongly discouraged,” and that there is “no scientific evidence that using smokeless tobacco can help a person quit smoking.” But this year it approved funding for a study that might provide some of that very evidence.

“Switch and Quit” is directed by Brad Rodu, a professor of medicine at the University of Louisville. He analyzed the 2000 National Health Interview Survey and found that male smokers who switched to smokeless tobacco were more likely to quit smoking than those who used nicotine patches or gum.

“Americans are largely misinformed about the relative risks. … They think smokeless tobacco is just as dangerous,” Rodu said. “This level of misinformation is an enormous barrier to actually accomplishing tobacco-harm reduction because if people believe that the products have equal risk, there’s not a real incentive.”

The program is funded through Rodu’s research money, which includes grants from the tobacco industry. Grants through the University of Louisville are unrestricted, which the program says “ensures the scientific independence and integrity of research projects and activities.”

“There’s absolutely no influence whatsoever,” Rodu said. “I decide, along with my colleagues, how we use the money, for what projects, and this is entirely the case. I would not have a situation where there was some control over the kind of projects I undertake.”

Tobacco companies want to market more smokeless tobacco and other cigarette alternatives to make up for falling cigarette sales. Some have introduced “snus” — small pouches like tea bags that users stick between the cheek and gum — and dissolvable tobacco — finely milled tobacco shaped into orbs, sticks and strips.

But they’re barred by federal law from explicitly marketing them as less risky than cigarettes — at least for now. That means the “Switch and Quit” program can do something the tobacco industry itself cannot: claim that smokeless tobacco has a health benefit when compared to smoking.

The program says smoking kills about 220 adults a year in and around Owensboro. The state of Kentucky, a leading tobacco grower, has the nation’s highest smoking and lung cancer rates.

Owensboro and the surrounding area consume about 3 million cigarettes a week, according to the program. That amounts to well over a pack for every man, woman and child in the community of about 115,000 people.

Owensboro resident Vernon Goode had smoked for about 10 years before he recently traded his Marlboros for dissolvable tobacco tablets. The campaign didn’t inspire him to quit, but he said he thought it was a good idea.

“I was just wanting to quit because, you know, I could feel it in my lungs,” Goode said. “I’ll smoke a cigarette every once in a while, but not very often. I want to quit altogether and I’m just using this right here as I guess what you’d call a stepping stone.”

The Owensboro program has raised concerns among some in the public health community who say organizers are claiming smokeless tobacco is a healthier alternative to smoking without approval from the Food and Drug Administration.

A 2009 law gives the FDA authority to evaluate health risks of tobacco products and approve those that could be marketed as safer than what’s currently for sale. None have been given the OK yet. The FDA also plans to regulate electronic cigarettes, battery-powered plastic and metal devices that heat a liquid nicotine solution in a disposable cartridge, creating vapor that users inhale.

Matthew Myers, president of the Campaign for Tobacco-Free Kids, called the program “a giant experiment with the people of Owensboro without rules or guidance designed to protect individuals from experimental medicine.”

Smokeless tobacco isn’t a safe alternative to cigarettes, according to the Centers for Disease Control and Prevention. Health warnings on the products required by the FDA state the same thing.

However, some studies, including a 2007 report from the Royal College of Physicians in London titled “Harm Reduction in Nicotine Addiction,” suggest that some smokeless tobacco products are about 90 percent less harmful than cigarettes.

“The worst that you can say about smokeless tobacco is that it’s the lesser of two evils,” said Dr. Randall Thomas, an oncologist with the Owensboro Medical Health System. The health system, the community’s largest employer, is going smoke-free in 2013 and is offering Rodu’s program as one of a variety of quit-smoking tools for its employees.

“I don’t think we have any problem in telling a person that drinks a six-pack a day that if they could cut it back to two beers a day or two drinks a day that their health risks are greatly reduced,” Thomas said. “Finding a way to let people have their nicotine that carries less risk, it’s the realistic solution.”

The Owensboro program doesn’t suggest pharmaceutical nicotine replacement gum or patches. That’s because they are regulated to provide very small doses of nicotine and are recommended for only a short period of time, while smokeless tobacco can be used as long as a smoker needs, Rodu said.

Myers, of the Campaign for Tobacco-Free Kids, said more research is needed before anyone should suggest that the nation’s 46 million smokers would be better off using smokeless tobacco. In the meantime, he said, there are a host of FDA-approved products that can help people give up smoking.

“There’s a right way and a wrong way to determine whether smokeless tobacco can and should be marketed as a way to help people quit,” Myers said.

The National Cancer Institute approved funding earlier this year for a nationwide 1,250-person study to look at whether being given a snus product changes the habits of smokers who are not motivated to quit.

The tobacco industry sees smokeless tobacco as its future, said Matthew J. Carpenter, a psychology professor at the Medical University of South Carolina who is conducting the yearlong study.

Carpenter said the snus study will examine what smokers do when given smokeless tobacco. He won’t look at the health effects, or advise smokers to use the snus to quit.

“They are probably safer than conventional cigarettes, if for no other reason than you’re not burning anything, you’re not smoking anything, you’re not inhaling any smoke,” he said.

“If you compare it to conventional cigarettes, they’re probably a little bit better. If you compare it to quitting, they’re absolutely worse.”

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

New HPV Study Proves Vaccine’s Effectiveness

Source: Cancer.gov

A flurry of new research findings on a vaccine that prevents persistent infections by cancer-causing types of the human papillomavirus (HPV) has confirmed the vaccine’s efficacy and opened new avenues for research. The results, published in three separate reports, suggest that the vaccine could be simpler to administer and more affordable than researchers had previously thought—and that the vaccine may also have unexpected benefits.

All three studies originate from an ongoing clinical trial of Cervarix in Costa Rica. The new findings could help inform efforts to develop vaccination programs to prevent cervical cancer in countries around the world, the researchers said.

“The results from our trial and from other trials are extremely promising for this vaccine,” said Dr. Allan Hildesheim of NCI’s Division of Cancer Epidemiology and Genetics (DCEG), a leader of the trial. “And they suggest that the impact of the vaccine may go beyond cervical disease.”

HPV infections can lead to cancers of the anus, vagina, vulva, penis, and some oropharyngeal cancers, in addition to cervical cancer. Cervarix is one of two HPV vaccines currently approved by the Food and Drug Administration to prevent these infections; the other is Gardasil.

One of the studies found that fewer than the prescribed three doses of Cervarix may offer the same protection as the full course. If confirmed, this could make vaccination easier to administer and more affordable, factors that are especially important in developing countries that have high rates of cervical cancer.

A second study from the Costa Rica HPV Vaccine Trial found that the vaccine may protect against anal HPV infections that could eventually lead to anal cancer. (See “Clinical Trial Shows Potential Benefit of HPV Vaccine for Anal Cancer.”)

Vaccine May Protect against Additional HPV Types

The third study confirmed that the vaccine is highly effective in preventing persistent infections with HPV types 16 and 18—the types targeted by Cervarix. The researchers also found evidence of “cross-protection” against other cancer-causing HPV types not targeted by the original formulation—HPV types 31, 33, and 45.

Testing an HPV Vaccine in the “Real World”The safety and effectiveness of Cervarix and the other FDA-approved HPV vaccine, Gardasil, were established in clinical trials sponsored by the vaccine makers. Nonetheless, NCI researchers and their long-time collaborators in Costa Rica decided to conduct an independent study of a vaccine in a real-world setting.A goal of the community-based trial was to collect data that could help with the implementation of cervical cancer prevention programs, said Dr. Herrero. “Our results could help the people who are planning vaccination programs to use this expensive vaccine in the most effective way possible.”

Launched in 2004, the randomized trial includes 7,466 women between the ages of 18 and 25 from two Costa Rican communities (approximately one-third of the women in the region). Participants initially received Cervarix or a vaccine against hepatitis A. At the end of 4 years, the researchers offered the HPV vaccine to women in the control group.

The researchers will continue to follow the participants. “This community-based trial provides avenues to study not just the theoretical efficacy of the vaccine but the impact of vaccination on a well-defined population,” said Dr. Hildesheim.

“This is a potential additional benefit from vaccination that we had not considered initially,” said Dr. Hildesheim, noting that suggestive evidence for cross-protection has been reported previously.

The third study, published online September 9 in Cancer Discovery, also provided further evidence that the benefit of vaccination is greatest when the vaccine is given to young women before they have initiated sexual activity.

“Exposure to HPV occurs as soon as sexual activity begins, so if you start vaccination after that point, you will miss an opportunity to prevent infections,” said the study’s lead author, Dr. Rolando Herrero, formerly the study director in Costa Rica and now with the International Agency for Research on Cancer.

The findings on age are consistent with previous studies, noted Dr. Kevin Ault of Emory University’s School of Medicine, who studies HPV but was not involved in the study. “As you age, you accumulate exposures to HPV, and, if the vaccine is given after you’ve been exposed to the virus, then it’s not going to be effective.”

Fewer Doses May Offer Protection

The discovery that two doses—and possibly even one—of Cervarix may protect against infection was possible because the study was done in a “real world” community setting. Many women in the trial (approximately 20 percent) received only one or two doses, often because of pregnancy or an unrelated health problem.

The researchers found, however, that all of the women who received the vaccine were protected equally—at least for the first 4 years after vaccination. Those results appeared online in the Journal of the National Cancer Institute on September 9.

“This study is terrific proof of concept,” said Dr. Eduardo Franco of McGill University’s Faculty of Medicine, who also studies HPV and was not involved in the research. “It suggests that countries could adopt the suboptimal dose regimens and still receive the same protection as the full course, assuming that the protection against lesions will also hold.”

At the end of 4 years, the researchers offered the HPV vaccine to women in the control group. The researchers will follow the trial participants to determine how long the protection lasts.

If the current results are confirmed, the costs of vaccination programs could drop. “Our results may have important implications for public health, although many questions remain unanswered,” said the study’s first author, Dr. Aimée Kreimer of DCEG.

For instance, how long one or two doses of the vaccine protect against HPV infection is not known. In addition, the findings may not apply to other vaccines or to other populations, such as people who are malnourished or lack strong immune responses, the study authors cautioned.

More Affordable and Sustainable Cervical Cancer Prevention

Costa Rica HPV Vaccine Trial team
The Costa Rica HPV Vaccine Trial team in Guanacaste, Costa Rica, at the start of the study in 2004.

“The importance of the current study is not so much for Costa Rica, which has cervical cancer screening programs, but for countries that have truly high incidences of cervical cancer and no screening,” Dr. Franco said. More follow-up is needed to show that the suboptimal doses translate into fewer cervical precancerous lesions for vaccinated women, he added.

This study “represents an important step on the road to more affordable and sustainable cervical cancer prevention programs,” wrote Dr. Cosette Marie Wheeler of the University of New Mexico in an accompanying editorial.

Few, if any, developing countries where cervical cancer is common can afford vaccination programs, said Dr. Herrero. But if countries can afford to vaccinate only certain groups, they need to know which ones would benefit most, he noted. As the current study shows, this group would likely be young women who are not yet sexually active.

“When we started more than 25 years ago, we were just discovering that HPV was the cause of cervical cancer,” said Dr. Herrero. “Today we have a tremendous amount of tools and knowledge, which make it possible to intervene in this disease.”

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

2011-09-27T11:19:48-07:00September, 2011|Oral Cancer News|

New Study for Cancer Patients to Help Improve the Body’s Ability to Fight Illness

Source: Sign On San Diego

A Santa Monica research center will test an experimental therapeutic filtering device being developed by Aethlon Medical on blood taken from cancer patients, the San Diego company said Wednesday.

The study will target exosomes, bubbles of protein and RNA molecules excreted by cancerous cells that can block immune system cells from fighting the illness.

By removing exosomes from circulating blood, Aethlon officials hope their device will improve the body’s ability to fight cancer and the effectiveness of treatments such as chemotherapy.

Blood taken from 25 patients with non-small cell lung cancer, prostate cancer, melanoma, sarcoma, and head and neck cancer will be circulated through the Hemopurifier device.

In clinical use, blood would be filltered directly from the patient and returned to the body in a similar way to kidney dialysis.

However, in the newly announced pre-clinical trial blood will not be returned to patients, Aethlon Chairman and Chief Executive Officer James Joyce said.

“If we validate that our Hemopurifier is efficient in capturing exosomes, its possible that we could transition towards a human treatment study to evaluate exosome clearance from the entire circulatory system,” he said.

The test will be conducted by the Sarcoma Oncology Center, a nonprofit independent research institute focused on cancer therapy development.

“This clinical histological study is a critical validation step in Aethlon’s Hemopurifier strategy for cancer,” said Dr. Sant Chawla, the trial’s chief investigator. “The concept of ‘subtractive therapy’, eliminating a major mechanism of tumor progression and resistance to drugs, represents a potential breakout solution that needs to be tested in the clinic.”

The trial will involve 25 patients and will cost just under $75,000, Aethlon officials said.

The filtering system works by pumping blood through a cartridge containing 2,800 hollow fibers that are perforated by tiny holes measuring about 250 nanometers.

Plasma and red and white blood cells pass through the holes and return to the circulatory system while exosomes and other larger particles, such as viruses, are trapped.

The Hemopurifier was cleared by U.S. regulators in 2007 for safety testing to counteract bioterrorism agents.

Last year, the company launched a study of the system on hepatitis C patients in India with the Medanta Medicity Institute near New Delhi.

In May, Aethlon asked the Food and Drug Administration to approve a Phase 1 clinical trial of the device on hepatitis C patients in the United States.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Shortchanging cancer patients

Source: nytimes.com
Author: Ezekiel J. Emanuel

Right now cancer care is being rationed in the United States.

Probably to their great disappointment, President Obama’s critics cannot blame this rationing on death panels or health care reform. Rather, it is caused by a severe shortage of important cancer drugs.

Of the 34 generic cancer drugs on the market, as of this month, 14 were in short supply. They include drugs that are the mainstay of treatment regimens used to cure leukemia, lymphoma and testicular cancer. As Dr. Michael Link, the president of the American Society of Clinical Oncology, recently told me, “If you are a pediatric oncologist, you know how to cure 70 to 80 percent of patients. But without these drugs you are out of business.”

This shortage is even inhibiting research studies that can lead to higher cure rates: enrollment of patients in many clinical trials has been delayed or stopped because the drugs that are in short supply make up the standard regimens to which new treatments are added or compared.

The sad fact is, there are plenty of newer brand-name cancer drugs that do not cure anyone, but just extend life for a few months, at costs of up to $90,000 per patient. Only the older but curative cancer drugs — drugs that can cost as little as $3 per dose — have become unavailable. Most of these drugs have no substitutes, but, crazy as it seems, in some cases these shortages are forcing doctors to use brand-name drugs at more than 100 times the cost.

Only about 10 percent of the shortages can be attributed to a lack of raw materials and essential ingredients to manufacture the drugs. Most shortages appear instead to be the consequence of corporate decisions to cease production, or interruptions in production caused by money or quality problems, which manufacturers do not appear to be in a rush to fix.

If the laws of supply and demand were working properly, a drug shortage would cause a price rise that would induce other manufacturers to fill the gap. But such laws do not really apply to cancer drugs.

The underlying reason for this is that cancer patients do not buy chemotherapy drugs from their local pharmacies the way they buy asthma inhalers or insulin. Instead, it is their oncologists who buy the drugs, administer them and then bill Medicare and insurance companies for the costs.

Historically, this “buy and bill” system was quite lucrative; drug companies charged Medicare and insurance companies inflated, essentially made-up “average wholesale prices.” The Medicare Prescription Drug, Improvement and Modernization Act of 2003, signed by President George W. Bush, put an end to this arrangement. It required Medicare to pay the physicians who prescribed the drugs based on a drug’s actual average selling price, plus 6 percent for handling. And indirectly — because of the time it takes drug companies to compile actual sales data and the government to revise the average selling price — it restricted the price from increasing by more than 6 percent every six months.

The act had an unintended consequence. In the first two or three years after a cancer drug goes generic, its price can drop by as much as 90 percent as manufacturers compete for market share. But if a shortage develops, the drug’s price should be able to increase again to attract more manufacturers. Because the 2003 act effectively limits drug price increases, it prevents this from happening. The low profit margins mean that manufacturers face a hard choice: lose money producing a lifesaving drug or switch limited production capacity to a more lucrative drug.

The result is clear: in 2004 there were 58 new drug shortages, but by 2010 the number had steadily increased to 211. (These numbers include noncancer drugs as well. )

Unfortunately, there is no quick fix, because all solutions require legislation. A bill introduced in February by Senator Amy Klobuchar, Democrat of Minnesota, and Senator Bob Casey, Democrat of Pennsylvania, would require generic manufacturers to notify the Food and Drug Administration if they expected a supply problem or planned to stop manufacturing a drug. But the F.D.A. isn’t able to force manufacturers to produce a drug, and learning about impending shortages with little authority to alleviate them is of limited benefit. Indeed, early warning could exacerbate the problem: the moment oncologists or cancer centers hear there is going to be a shortage of a critical drug, their response could well be to start hoarding.

You don’t have to be a cynical capitalist to see that the long-term solution is to make the production of generic cancer drugs more profitable. Most of Europe, where brand-name drugs are cheaper than in the United States, while generics are slightly more expensive, has no shortage of these cancer drugs.

One solution would be to amend the 2003 act to increase the amount Medicare pays for generic cancer drugs to the average selling price plus, say, 30 percent, after the drugs have been generic for three years. This would encourage the initial rapid price drop that makes generics affordable, but would allow for an increase in price and profits to attract more generic producers and the fixing of any manufacturing problems that subsequently arose.

Increasing the price for generic oncology drugs would have a negligible impact on overall health care costs. Total spending on generic injectable cancer drugs was $400 million last year — just 2 percent of cancer drug costs, and less than 0.5 percent of the total cost of cancer care. If we are worried about costs, we could follow Europe and pay for the higher prices by lowering what Medicare pays for the brand-name drugs that extend life by only a few months.

A more radical approach would be to take Medicare out of the generic cancer drug business entirely. Once a drug becomes generic, Medicare should stop paying, and it should be covered by a private pharmacy plan. That way prices can better reflect the market, and market incentives can work to prevent shortages.

Scare-mongering about death panels and health care reform has diverted attention from real issues in our health care system. Shortages in curative cancer treatments are completely unacceptable. We need to stop the political demagoguery and fix the real rationing problem.

1. Ezekiel J. Emanuel is an oncologist and former White House adviser who will be a professor of medical ethics and health policy at the University of Pennsylvania beginning in September.

Sanford researcher to study new oral cancer therapy

Source: www.mdnews.com
Author: public release

A new Sanford clinical trial will study the safety and effectiveness of a drug treatment on patients receiving radiation and chemotherapy for head and neck cancer.

About three to five percent of all cancers reported in the United States are head and neck cancers. Although the incidence of this type of cancer is relatively low, survival rates are poor — with about a 50 percent of patients surviving over the five-year period following diagnosis, according to John Lee, MD, FACS, Principal Investigator of the trial and a Sanford Clinic Ear, Nose and Throat specialist.

Lee’s early research led to the discovery that mice treated with the generic drug dichloroacetate (DCA) responded to cancer therapy 30 percent better. He has received approval from the Food and Drug Administration to begin a clinical trial with patients who are receiving treatment for head and neck cancer. The trial will be open to Sanford patients, and others nationwide.

“We are proud of and continue to encourage innovative clinical trials at Sanford that helps us further understand the molecular, cellular and genetic basis of cancer,” said David Pearce, PhD, Vice President, Sanford Research in Sioux Falls.

Dr. Lee, who was honored in 2010 by the American Cancer Society for his research, has been studying the link between the Human Papilloma Virus (HPV) and the development of head and neck cancers. His research team has tested the treatment of head and neck tumors in mice finding that factors that enhanced the immune system seemed to improve the rates of survival.

DCA is being used in several ongoing clinical trials nationwide after a recent publication showed potential improvement for this drug in animal studies. The drug, which has been used in human patients with metabolic disorders, inhibits an enzyme called pyruvate dehydrogenase kinase (PDK) which is involved in the metabolic pathways at the cellular level. PDK is over expressed in many types of cancer, including the head and neck cancer that is part of this new clinical trial. The trial will evaluate how altering cell metabolism will affect the outcome for participants.

Dr. Lee has developed a placebo-controlled research study (a study in which a percentage of participants take an inactive substance that looks the same as active medications). All participants will receive the standard treatment for head and neck cancer and will, in addition, receive either the placebo or the study drug. This study will be masked, meaning the participant, study doctor and study coordinator are blinded to what the participant is taking. Participants will be monitored closely during treatment by their cancer doctors and Sanford Research staff.

A total of 50 patients will be enrolled in the clinical trial. After an initial screening, some patients will receive DCA as an oral medication or through a gastrointestinal tube twice a day for eight weeks. Others will receive placebos over the same period. During that time, participants will be given treatments of Cisplatin (a chemotherapy drug) and undergo radiation therapy. The participants’ progress will be followed over five years.

The new trial will study not only the safety of delivering DCA during treatment, but also assess the local response rate, overall survival and relative toxicities for participants participating in the study. Researchers also hope to evaluate participants’ HPV status and immune response levels and correlate those findings as part of the trial. Participants will also be evaluated for differences in health-related quality of life.

New labels may not go far enough

Source: www.denverpost.com
Author: Rhonda Hackett

How far would you go to stop a killer?
Smoking continues to kill more Americans every year than alcohol, AIDS, car accidents, illegal drugs, murders and suicides combined. Tobacco use remains the leading preventable cause of death and the single greatest driver of health-care costs in Colorado.

Despite concerted efforts over recent years to educate people about the dangers of tobacco use, 46.6 million American adults smoke, while kids alone are responsible for roughly $2 billion in annual cigarette sales revenues.

More than 400,000 people die every year from tobacco use (4,300 in Colorado), while an additional 50,000 adults die as a result of second-hand smoke exposure. More than 8 million Americans currently suffer from tobacco- caused illnesses, resulting in an estimated $96 billion in public and private health care expenditures each year. In Colorado, the tab is about $1.3 billion per year.

Simply put, tobacco is the single most lethal and costly legal commodity available in America today.
The U.S. Food and Drug Administration has now followed the lead of other developed nations by requiring cigarette packages carry graphic warning labels. FDA Commissioner Margaret Hamburg said at a White House briefing, “We want kids to understand smoking is gross – not cool – and there’s really nothing pretty about having mouth cancer.”

Critics of the warning labels cite the fact that smoking is a legal activity and as such products associated with it should not be subject to government mandate discouraging use. The Institute of Medicine rebuts this stance, stating “Even though tobacco products are legally available to adults, the paramount public health aim is to reduce the number of people who use and become addicted to these products, through a focus on children and youths. The warnings must be designed to promote this objective.”

For years, the tobacco industry has argued smokers are adequately informed about the dangers of tobacco. Studies have clearly demonstrated, however, that nothing could be further from the truth. Regardless of the many public education campaign efforts and widely discussed reports on the dangers of tobacco, most smokers have limited knowledge about the health effects of their habit. Few realize it is directly related to heart disease, and fewer still know of its connection to strokes, impotence, respiratory illnesses and complications during pregnancy.
Critics have also argued the warning labels don’t really work, citing mixed results of similar programs in other countries. Graphic warning labels have been instrumental in increasing the public’s knowledge about the harmful effects of smoking in more than 30 countries for the past 10 years. Geoff Fong, a global health researcher at the University of Waterloo in Canada, states graphic warning labels are directly linked to “more negative attitudes toward tobacco and cigarettes, greater knowledge about the harms of cigarettes depicted in those warnings, and an increased motivation to quit.”

Tobacco companies spend about $35 million per day advertising their products – $12.8 billion per year. They reap the rewards of untold profits, selling a consumer product that kills half its users. Requiring tobacco companies to boldly display attention-grabbing images of the undisputed effects of its use is no different than including appropriate warnings on any product.

Then again, maybe it is. While lawnmowers now carry a warning including images advising the operator that putting a hand into moving parts can result in injury, millions of people are not harmed by this activity every year. Moreover, taxpayers are not left on the hook for hundreds of billions of dollars because of the ill effects of any other free-enterprise merchandise.
The graphic images will not stop smoking altogether. But other countries have learned they are an integral part of an effective anti-smoking campaign. America cannot afford not to follow suit.

1. Rhonda Hackett of Denver is a clinical psychologist.

Cigarette ads, packages must include oral cancer warnings, says FDA

Source: http://www.healthcanal.com/
Author: Craig Palmer, ADA News staff

The Food and Drug Administration will require use of a “cancerous lesion on lip” image in cigarette advertising and packaging for its potential to motivate positive behavioral change, influence youth and young adults in particular and inform the public that cigarettes cause oral cancer.

Flexing its regulatory muscle on the second anniversary of the Family Smoking Prevention and Tobacco Control Act, which was signed into law June 22, 2009, the FDA unveiled nine graphic health warnings to be placed on all cigarette packs, cartons and ads no later than Sept. 22, 2012.

“The nine new health warning statements and the accompanying graphic images selected by FDA convey information that is factual and uncontroversial,” the agency said in the regulatory notice.

The FDA simultaneously announced a public inquiry and request for comments on the public health impact of modified risk tobacco products sold or distributed for use to reduce harm or the risk of tobacco-related disease associated with commercially marketed tobacco products. The FDA scheduled a public forum Aug. 25-26 to obtain information on “the scientific issues associated with assessment and ongoing review of MRTPs.” These include smokeless and other products promoted as alternatives to cigarette smoking.

The Association supported the 2009 tobacco control law, and has advised the FDA on using the law to shape public tobacco policy. “Dentists are the first line of defense in the war against oral cancer and many other tobacco-related diseases,” the Association told the FDA in commenting on tobacco product regulation.

“As a matter of public health, we have become increasingly alarmed by recent attempts to market smokeless tobacco as a healthier (or less harmful) alternative to cigarettes,” the Association’s Oct. 9, 2009 statement said. “Smokeless tobacco is not a healthy alternative to cigarette smoking; both products pose health risks.”

FDA issued the requirement for larger, graphic health warnings for cigarette packages and advertisements in a June 22, 2011 Federal Register document dense with analysis and research rejecting tobacco industry arguments against the proposal and explaining how and why these images and warnings will get public attention and reduce smoking-related disease and death.

An image the FDA describes as “cancerous lesion on lip” will illustrate a “WARNING: Cigarettes cause cancer” statement chosen, the agency said, for scoring high in focus group testing on emotional and cognitive reaction scales and a “difficult to look at” measure.

“First, ‘cancerous lesion on lip’ was the only image among the images proposed for use with this warning statement that had a positive impact on beliefs about the health risks of smoking and secondhand smoke exposure in one of the study samples (adults viewing a hypothetical advertisement),” the FDA said in the regulatory document.

“Furthermore, as is stated in several comments…the selected image ‘cancerous lesion on lip’ is likely to have particular relevance for youth. As explained in some of these comments, the research literature suggests that youth are likely to relate to and be susceptible to cigarette warnings depicting the negative short-term impacts of smoking on their personal appearance, including their lips and teeth.

“Several comments noted that the image could be especially effective with younger audiences and could positively influence such audiences by illustrating how the health effects caused by smoking negatively affect their physical appearance. The comments indicated that adolescents can relate to and will be susceptible to this message.

“We agree with these comments,” the FDA said in responding to the comments on image effectiveness. “It is important to include content in the required warnings that is relevant to youth. The image ‘cancerous lesion on lip’ has the potential to positively impact youth behavior in addition to adult and young adult behavior.”

The FDA disagreed with comments that the image was “too gross” to be effective and that oral cancer was an odd choice of cancers to depict in the graphic warning, noting that “the research literature indicates that images that evoke strong emotional reactions can promote greater awareness and better recollection of the health risks of smoking and can increase the likelihood smokers will reduce their smoking, make an attempt to quit, or quit altogether.

“Furthermore, the choice of cancers depicted in the required warning is appropriate and will help inform the public that cigarettes cause oral cancers and thus increase public awareness of the negative consequences of smoking.”

The National Tobacco Quitline phone number, 1-800-QUIT-NOW, must accompany the nine new warnings.

Information for professionals and the public to assist in tobacco cessation efforts can be found on ADA.org.

Immunity Drugs Used to Fight Cancer

Source: The Wall Street Journal

Scientists are scrambling to develop medications that fight cancer by spurring the body’s immune system, a form of treatment that some cancer specialists believe may hold the key to keeping a patient permanently disease-free.

The new efforts come in the wake of recent Food and Drug Administration approvals of Dendreon Corp.’s Provenge, an immunotherapy drug used to treat prostate cancer, and Bristol-Myers Squibb Co.’s Yervoy, for melanoma.

Other immunotherapy drugs are being developed for a number of other cancers, including lung, brain and kidney cancers. Unlike most traditional therapies that attack a cancer directly, immunotherapy uses the body’s own internal defenses to ward off the disease, with the ultimate hope of building up a long-term resistance to the cancer.

“If we are ever going to use the word ‘cure’, the immune system is going to have to come into play,” says Stephen Hodi, director of the melanoma center at Dana-Farber Cancer Institute in Boston.

One of the ways that cancer survives and ultimately spreads through the body is by exploiting a function in all cells that prevents the immune system from killing them. Researchers have found that cancer cells have multiple methods of avoiding detection and suppressing the immune system’s response.

“Why would cancer devote so much energy to avoid the immune system if the immune system didn’t have the potential to reject the cancer?” says Robert Vonderheide from the Abramson Cancer Center of the University of Pennsylvania.

There are big hurdles to advancing the field of immunotherapy. Some of the drugs have significant side effects. And the complex treatments are among the priciest in health care. Yervoy costs about $120,000 for a course of treatment and Provenge $93,000.

The growing interest in immunotherapy comes even as traditional cancer-targeting drugs have become more effective. Still, such drugs often just delay the ultimate recurrence of the disease as tumors develop resistance to the treatment, or some cancer cells survive the therapy and regrow. The hope is that the immune system’s long-term activity against the cancer could stop this cycle.

Varied Approaches
Immunotherapies can work in several ways. They can help the immune system increase its response so that it fights the cancer better; they can stop cancers from slowing down or halting the immune system’s activation; or they can help the immune system find the tumor and kill it.

Provenge, which received FDA approval last year, is made by combining some of the patient’s own immune cells with a specific protein that is created by most prostate cancers. Although the exact mechanism isn’t fully understood, the drug, when given intravenously to the patient, is believed to activate other immune cells to see the cancer as a threat and attack it.

Yervoy is an antibody that binds to a molecule on certain immune-system cells that block them from becoming active. The addition of Yervoy allows the immune cells to become active and fight the cancer.

FDA approvals for Provenge and Yervoy helped set the stage for the current bout of drug research. “We don’t have to convince people this is a good idea,” says Ira Mellman, vice president of research oncology at Roche Holding AG’s Genentech unit, which says it is developing immunotherapy drugs that target advanced solid tumors.

Bristol-Myers Squibb, maker of Yervoy, is investigating the drug’s possible use for other cancers, including prostate and lung. And Dendreon is developing a drug for bladder cancer that works similarly to Provenge.

Other companies are also working on immunotherapy drugs. Roche Holding AG says its research is targeting advanced solid tumors, while GlaxoSmithKline PLC is focusing on several cancers, including lung and melanoma.

Among smaller pharmaceutical companies, Oncothyreon Inc. is working with Merck KGaA on a lung-cancer treatment, and Agenus Inc. is developing therapies in areas including brain cancer and kidney cancer.

There are currently 23 cancer immunotherapies in pipeline development, according to market-research firm Decision Resources.

The FDA currently limits Provenge and Yervoy to patients with advanced forms of their disease and with few other treatment options. Clinical trials have shown that Provenge has minimal side effects, but Yervoy can trigger fatal allergic reactions in some patients.

Side effects will continue to be heavily scrutinized as the drugs are expected to be used earlier in the disease progression or to prevent relapse.

Trial and Error
The idea of using the immune system first drew significant research attention in the mid- to late-1990s, but multiple failures led to widespread discouragement, says Dr. Vonderheide.

Developments in recent years have produced the momentum that researchers believe will allow it to reach the next level of more powerful treatments and, ultimately, their combination with both traditional drugs and other immunotherapies, he says.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

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