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Experts: E-cigarette regulations necessary to balance potential benefits, unknown harms

Smoking cigarettes has long been established as the leading cause of preventable death in the United States.

The rapid growth in marketing and popularity of electronic cigarettes — which offer an alternative nicotine-delivery option to traditional, combustible tobacco products — has prompted a global public health debate.

E-cigarettes have been considered a less toxic alternative to combustible tobacco, and supporters have touted the devices as possible smoking cessation aids.

However, several medical societies — including ASCO and the American Association for Cancer Research (AACR) — have called for the regulation of e-cigarettes and other electronic nicotine delivery systems, emphasizing the need for additional research into their potential long-term adverse health effects. Further, studies have shown children can easily access the devices, prompting fears that they may serve as a gateway drug for nicotine addiction and lead to subsequent use of other tobacco products.

Evidence-based smoking cessation strategies should be preferred over the use of e-cigarettes, according to Matthew Steliga, MD, a thoracic oncologist in the department of surgery at the University of Arkansas for Medical Sciences.

Evidence-based smoking cessation strategies should be preferred over the use of e-cigarettes, according to Matthew Steliga, MD, a thoracic oncologist in the department of surgery at the University of Arkansas for Medical Sciences. “When a patient [asks about e-cigarettes], they are looking for acceptance and permission from the physician,” he said. “I don’t provide that. I tell them, ‘I don’t think it’s going to make you better. It sounds to me like you need help quitting.’”

Source: Photo by University of Arkansas for Medical Sciences

“I don’t see e-cigarettes as … making us healthy in any way,” Matthew Steliga, MD, a thoracic oncologist in the department of surgery at the University of Arkansas for Medical Sciences, told HemOnc Today. “This is not a product that is being pushed out by academia. It is a product being pushed out by industry. There are some countries where e-cigarettes are not permitted at all.”

The FDA proposed a new “deeming rule” in April 2014 that would allow it to regulate tobacco-related products — such as e-cigarettes, cigars, pipe tobacco, dissolvable products that are not “smokeless tobacco,” gels and waterpipe tobacco — under the Federal Food, Drug and Cosmetic Act.

The FDA told HemOnc Today it had received more than 135,000 public comments on the deeming proposal as of March. The final rule is expected in June.

“You hear statements about electronic cigarettes claiming that they may help,” Steliga said. “If that’s truly the case, then they should be considered a drug-delivery device and should be regulated by the FDA. So far, [e-cigarettes] have fallen through a lot of loopholes in regulation, oversight, distribution, sales and taxation.”

HemOnc Today spoke with oncologists and experts in tobacco-related cancers about whether e-cigarettes offer any health benefits to current smokers compared with traditional cigarettes, how a lack of data has influenced the public perception of the devices and how strictly they should be regulated by the FDA.

Gateway for addiction

Without FDA regulation of e-cigarettes, their popularity — and availability — continues to skyrocket.

E-cigarettes — or electronic nicotine delivery systems (ENDS) — were first introduced to the U.S. market in the early 2000s. At that time, they were distributed over the Internet through smaller, independent companies.

There are now more than 460 ENDS brands available online in more than 7,700 flavors, according to a joint policy statement from AACR and ASCO co-published in March in Journal of Clinical Oncology and Clinical Cancer Research.

Advertising for e-cigarettes also has exploded. Advertising sales for e-cigarettes increased from $5.6 million in 2010 to $82.1 million in 2013, according to a 2014 report published by Legacy, a public trust organization created as part of the Tobacco Master Settlement Agreement to study and educate the public about the impact of tobacco.

This increase in spending may be attributed to the fact that many e-cigarette brands are now owned by major tobacco companies, experts said. In addition, the use of advertising — as well as the variety of available flavoring options — suggest e-cigarette marketing is increasingly directed toward a younger audience.

“Chocolate, strawberry, bubble gum, gummy bear-flavored nicotine fluid?” Steliga said. “Who are you marketing that toward? By candying it up, not only does it appeal to younger people, but it also makes it seem safer and distances it from tobacco. That is a big, big worry.”

A study by Bunnell and colleagues, published in August 2014 in Nicotine and Tobacco Research, showed the number of middle school-aged to high school-aged youth who had never smoked a cigarette but who used an e-cigarette increased threefold from 79,000 in 2011 to 263,000 in 2013. A study by Arrazola and colleagues, published in April in Morbidity and Mortality Weekly Report, indicated current use of e-cigarettes among middle and high school students tripled — from 4.5% to 13.4% — from 2013 to 2014.

Eric J. Jacobs, PhD

Eric J. Jacobs

“Regulation of e-cigarettes is urgently needed; a nicotine addiction warning is not enough,” Eric J. Jacobs, PhD, strategic director of pharmacoepidemiology for the American Cancer Society, told HemOnc Today. “One important recommendation from [the AACR/ASCO policy statement] is restricting youth-oriented marketing of e-cigarettes, which would include [regulation of] strategies such as use of cartoon characters in advertising, sponsorship of rock concerts, and distribution of hats and T-shirts with e-cigarette brand logos. Another strategy is to require Internet and mail-order companies to verify age and not sell to minors.”

Williams and colleagues evaluated the ease with which minors could purchase e-cigarettes online. Results — published in March in JAMA Pediatrics — showed 11 nonsmoking minors aged 14 to 17 years made supervised e-cigarette purchase attempts from 98 vendors between February and June 2014. Researchers reported 76.5% of these orders were delivered successfully, with no attempts to verify the purchasers’ ages at the time of delivery.

“The most worrisome thing is that it renormalizes smoking,” Steliga said. “This could try to make smoking more acceptable, especially for youth who are nonsmokers. When you take your first drag on a cigarette as a youth, it’s probably going to make you cough and it isn’t a pleasant experience. I worry that any youth who initiate their addiction by these ENDS are being drawn in by novelty and technology. Once introduced to nicotine, cigarettes could follow.”

Bunnell and colleagues demonstrated that a higher percentage of youth who had smoked e-cigarettes than never users intended to smoke conventional cigarettes (43.9% vs. 21.5%). Overall, e-cigarette users were significantly more likely to have smoking intentions than never users (adjusted OR = 1.7; 95% CI, 1.24-2.32).

Jamie S. Ostroff, PhD

Jamie S. Ostroff

“The most important regulations have to come about for youth use,” Jamie S. Ostroff, PhD, chief of behavioral sciences service and director of the tobacco treatment program at Memorial Sloan Kettering Cancer Center, told HemOnc Today. “The current lack of regulation of e-cigarettes allows there to be a resurgence of the advertisements that were promulgated in the 1960s and 1970s. Anyone who is even a casual historian of tobacco control knows that those ads were highly effective and highly resourced. There are a lot of questions about the safety and potential benefits of e-cigarettes, but FDA regulation guided by a clear understanding of youth attitudes and use patterns is perhaps the most critical need for prevention of tobacco-related morbidity and mortality.”

Need for regulation

When the FDA’s “deeming rule” is finalized, the agency will be able to immediately begin regulation of e-cigarettes.

“Public health-based regulation of these products can help reduce the death and disease toll from tobacco use, and help FDA protect public health by requiring the review of new tobacco products and health-related claims for regulated tobacco products in today’s rapidly evolving marketplace,” the agency stated in an email to HemOnc Today.

The FDA’s draft proposal would require manufactures of e-cigarettes to register their products with the FDA and report product and ingredient listings; adhere to minimum age and identification restrictions to prevent sales to underage youth; include health warning labels; and only market new tobacco products after FDA review. The regulation also would ban the distribution of free samples, vending machine sales in facilities that admit youth, and use of reduced-risk claims such as “light” or “mild” unless the manufacturer provides valid scientific data to support such claims and is granted an FDA market authorization.

Graham Warren, MD, PhD

Graham Warren

“I think that’s a good start,” Graham Warren, MD, PhD, vice chairman for research in radiation oncology at Medical University of South Carolina and chair of ASCO’s Tobacco Cessation and Control Subcommittee, which helped develop the AACR/ASCO joint statement on e-cigarettes, told HemOnc Today. “The problem is, we don’t know what the health effects of e-cigarettes are. It’s very difficult to think that they are worse than smoking, but we don’t have data on that yet. At the same time, they are going to be more harmful than not using e-cigarettes at all, so there’s going to be some adverse health effects associated with them we need to figure out.”

The fact that there are so many different types of e-cigarettes may complicate regulation and data collection, Warren said.

“One of the biggest problems we have to contend with is that there are hundreds of different e-cigarette products with thousands of variations — even though there are not as many compounds as are in cigarette smoke — and the individual constituents of e-cigarette fluid can change, as well as how they are heated, vaporized and absorbed,” Warren said. “Due to the complexity of constituents in e-cigarettes, it is very difficult to try to say, ‘We know they are all going to behave the same way.’ We may find that one change in the chemical constituents in the liquid, heating element or the delivery system can dramatically alter behavior, absorption or health effects. That’s going to be a challenge for the FDA to accurately assess and regulate e-cigarettes.”

The FDA may not strictly regulate e-cigarettes until more research is available, thereby allowing for evidence-based reform, experts said.

Bruce E. Johnson, MD, professor of medicine in the department of adult oncology at Dana-Farber Cancer Institute and Harvard Medical School, told HemOnc Today that the FDA should treat e-cigarettes no differently than combustible cigarettes.

Bruce E. Johnson, MD

Bruce E. Johnson

“They should be regulated the same way as combustible cigarettes, although we’ve never been able to muster the will to regulate cigarette sales the way I think we should in the United States,” Johnson said. “With electronic cigarettes, we have a chance at a fresh start. But e-cigarettes are a two-headed monster. If electronic cigarettes are an effective means to help people stop smoking, they might be useful to people who are addicted to cigarettes. But, they are the third most common form of nicotine sources for people who have not graduated from high school after cigarettes and cigars. If they are more easily accessible than tobacco products, it has potential to start nicotine addiction in the younger population. So, when thinking about regulating them, you have to weigh both factors and populations.”

The FDA said it plans to weigh the risks and benefits, and then will address concerns raised during the comment period within its final rule.

“FDA knows that, though all tobacco products are potentially harmful and potentially addictive, different categories of tobacco products may have the potential for varying effects on public health,” the FDA told HemOnc Today in a statement. “Regulating these products allows FDA to properly understand the relative impacts of the product categories, and to evaluate how individual products in each category may affect public health.”

Benefits vs. harms

Overall, the regulation of e-cigarettes may prove challenging due to a lack of data.

Along with the need to better understand the potential harms of e-cigarettes, any claims that e-cigarettes are effective smoking cessation aids would be premature, Ostroff said.

“There are different types of adult users,” Ostroff said. “There are some people who are finding that e-cigarettes are an acceptable replacement for smoking and are quitting combustible cigarettes altogether. There are others who are finding that e-cigarettes are partially acceptable, and they are dual smoking and successfully reducing their amount of combustible smoking. Then there are those who are dual using but aren’t changing their combustible smoking habits.”

A population-based study by Al-Delaimy and colleagues, published in April in American Journal of Public Health, did not support the use of e-cigarettes as smoking cessation aids. Results from 1,000 California smokers indicated those who also used e-cigarettes were 49% less likely to decrease traditional cigarette use and 59% less likely to quit smoking compared with smokers who did not use e-cigarettes.

Data also are needed to compare e-cigarettes with other smoking cessation aids.

“They haven’t been around nearly long enough to compare to nicotine replacements and antidepressants in treating nicotine addiction,” Johnson said. “The potential health implications of electronic cigarettes — namely their safety — haven’t been defined. Inhaling nicotine in a heated vapor is probably not good for you. It took almost 40 years since the introduction of mass-produced cigarettes before a link to lung cancer was made.”

Johnson cited multiple articles published in PLoS One in the last year that have presented preliminary evidence of inflammation and damage of the lungs associated with materials in e-cigarettes. One such study, conducted by Sussan and colleagues, used a mouse model to demonstrate that e-cigarettes impaired pulmonary antibacterial and antiviral defenses.

Yet, there still could be a public health benefit.

At the 2015 American Association for the Advancement of Sciences meeting, a presentation titled “E-Cigarettes: What’s the Real Medical Innovation Breakthrough?” by Kevin Bridgman, MD, chief medical officer of Nicovations — a subsidiary of British American Tobacco — suggested e-cigarettes could offer the same progressive step down from smoking as nicotine patches or gum, but with a greater appeal to smokers because of the similarity to traditional smoking.

Bridgman referenced a yet-to-be-published study conducted by Neilson and colleagues that used the EpiAirway (MatTek) model, a highly differentiated in vitro human epithelial tissue culture. In the study, cigarette smoke reduced cell viability to 12% at 6 hours, whereas e-cigarettes were associated with results similar to untreated air controls.

“There is growing consensus among public health professionals that e-cigarettes are significantly less risky than conventional cigarettes,” Bridgman said in a press release. “However, we believe that, in order to realize their full potential, e-cigarettes should be regulated to ensure appropriate quality and safety standards, whilst also allowing sufficiently wide retail availability, appropriate lifestyle positioning and flexibility for the rapid introduction of product innovation. This would provide greater confidence without stifling innovation while enabling these products to compete effectively with cigarettes.”

Still, e-cigarettes have not been marketed as cessation aids, perhaps because they are developed by the tobacco industry, experts said.

“The long-term health risks of e-cigarette use are not known,” Jacobs said. “Most researchers agree that because combustible cigarettes are so lethal, switching to exclusive use of e-cigarettes would likely be helpful. However, many people use both e-cigs and combustible cigarettes. One concern is that some combustible cigarette smokers may be less likely to quit if they can maintain their nicotine addiction by using e-cigs at work or in other places where smoking combustibles is banned.”

Oncologic concerns

The AACR/ASCO policy statement encouraged health care providers to direct patients who use tobacco products to choose evidence-based cessation tools until the long-term safety of e-cigarettes is established.

However, patients may ask their oncologists about e-cigarettes before these data become available.

“I get asked that question all the time and I tell patients, unfortunately, I can’t say with any certainty if e-cigarettes are safer, equivalent or worse,” Warren said.

In this scenario, rather than waiting years for mature trial data, it may be warranted to rely on information from preclinical studies, Johnson said.

“This is the one time where animal models can be applicable to the human condition, because we have decades of information about what happens to humans after long-term exposure to cigarette smoke and how it compares to animal models,” Johnson said. “I think we will be able to tell the relative impact [of e-cigarettes] on people’s lungs by vaping in animals in a shorter period of time.”

Ostroff, who co-authored the AACR/ASCO policy statement, concluded that she and her colleagues should work with patients with cancer to develop acceptable, evidence-based tobacco cessation treatment plans. Still, physicians cannot ignore that many patients are interested in using e-cigarettes as part of their efforts to quit smoking, she said.

“We have the responsibility to provide education and counseling about potential risks and benefits of e-cigarettes,” Ostroff said. “Smokers who want to quit want to be successful, and the available evidence supports use of behavioral counseling and cessation medications (eg, nicotine replacement therapies, varenicline [Chantix, Pfizer] and bupropion) that have undergone rigorous testing.”

Steliga, on the other hand, would rather his patients not consider e-cigarettes. Instead, he favors evidence-based strategies.

“There’s all kinds of people who smoke who want to quit,” he said. “If you survey people and ask them if they’d like to quit, more than half of them would say yes. However, nicotine is one of the most addictive substances known to man. Nicotine fluid is highly toxic. … We have secondhand smoke data, but we don’t have secondhand vapor data. Still, if it’s foreign material you are sucking into your lungs, it probably is not making your lungs better.”

Evidence-based smoking cessation methods do exist, Steliga said.

“When a patient [asks about e-cigarettes], they are looking for acceptance and permission from the physician,” he said. “I don’t provide that. I tell them, ‘I don’t think it’s going to make you better. It sounds to me like you need help quitting.’ I try to get them to meet with a counselor first who has expertise in tobacco cessation. In our cancer center, we have put a tobacco treatment specialist in the clinic who is there with me when I see the patient.”

Rather than help smokers quit, e-cigarettes could be a setback, diminishing some of the progress made in the effort to reduce smoking prevalence, Steliga said.

“There’s so much we don’t know and so much harm that can still be done [with e-cigarettes],” he said. “We are seeing a drop in lung cancer death — not because of some magic bullet cure, but because of a drop in lung cancer incidence. That’s happening because smoking rates are decreasing. That’s important. We need to get people to quit smoking using evidence-based strategies. There are too many unknowns about the long-term outcome of e-cigarettes.” – by Anthony SanFilippo

References:

Al-Delaimy W, et al. Am J Public Health. 2015;doi:10.2105/AJPH.2014.302482.

Arrazola RA, et al. MMWR. 2015;64:381-385.

Brandon TH, et al. J Clin Oncol. 2015; doi:10.1200/JCO.2014.59.4465.

Bridgeman K. E-cigarettes: Public health threat or opportunity? Presented at: American Association for the Advancement of Science meeting; Feb. 12-16, 2015; San Jose, Calif.

Bunnell RE, et al. Nicotine Tob Res. 2014;doi:10.1093/ntr/ntu166.

Hughes K, et al. BMC Public Health. 2015;doi:10.1186/s12889-015-1618-4.

Sussan TE, et al. PLoS One. 2015;doi: 10.1371/journal.pone.0116861.

Williams RS, et al. JAMA Pediatr. 2015;doi:10.1001/jamapediatrics.2015.63.

For more information:

Eric J. Jacobs, PhD, can be reached at the American Cancer Society, 250 Williams St., Atlanta, GA 30303; email: eric.jacobs@cancer.org.

Bruce E. Johnson, MD, can be reached at Dana Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215; email bejohnson@partners.org.

Jamie S. Ostroff, PhD, can be reached at Memorial Sloan Kettering Cancer Center, 641 Lexington Ave., 7th Floor, New York, NY 10022; email: ostroffj@mskcc.org.

Matthew Steliga, MD, can be reached at the University of Arkansas for Medical Sciences, Winthrop P. Rockerfeller Cancer Center, 4301 West Markham St., #713, Little Rock, AR 72205; email: masteliga@uams.edu.

Graham Warren, MD, PhD, can be reached at the Medical University of South Carolina, 165 Cannon St., #503, Charleston, SC 29403; email: warrengw@musc.edu.

Disclosure: The researchers report no relevant financial disclosures.

 

POINTCOUNTER

Are e-cigarettes a viable smoking cessation tool for patients with cancer?

POINT

E-cigarettes are indeed a viable alternative for patients with cancer who are smokers and who are unable to quit using other methods.

Michael B. Siegel, MD, MPH

Michael B. Siegel

There are several clinical trials that demonstrate that e-cigarettes are at least as effective as the nicotine patch for smoking cessation. With new innovations that have entered the marketplace recently, it is likely that the effectiveness of e-cigarettes has increased substantially from these early trials.

The advantage of e-cigarettes is that — unlike the nicotine patch and other cessation drugs — they address both the pharmacologic and behavioral aspects of smoking addiction. Nicotine replacement therapy only addresses the pharmacologic aspect of addiction — that is, the need for nicotine. But we know that smoking addiction involves a lot more than just the nicotine.

There are the hand motions, the physical sensation of the cigarette, the oral sensation, the throat hit, the social aspects of smoking, the associations of smoking with other behaviors — all of these contribute to making smoking one of the most addictive behaviors. The e-cigarette is really the first smoking cessation product that can address these behavioral and social aspects of smoking addiction, and it is for this reason that the product is so popular.

The tremendous growth in the sale of these products and the projections that these products may substantially replace cigarettes in the market are a testament to the fact that these products really work. There are thousands of smokers who have successfully quit by using e-cigarettes, and many others who have cut down substantially on the amount they smoke and greatly improved their health as a result. I don’t see any reason these alternatives should not be available to smokers, and especially to patients with cancer who really need to do something to end their smoking addiction as urgently as possible.

It would actually be tragic to withhold or otherwise discourage these patients from trying a product that could literally save their lives.

Michael B. Siegel, MD, MPH, is a professor in the department of community health sciences at Boston University School of Public Health. He can be reached at Boston University School of Public Health, 801 Massachusetts Ave., Crosstown Center, Boston, MA 02118; email: mbsiegel@bu.edu. Disclosure: Siegel reports no relevant financial disclosures.

COUNTER

More data are needed before we should recommend e-cigarettes to our patients.

Michael Steinberg

Michael B. Steinberg

As someone who cares for patients with cancer, I can appreciate the appeal of e-cigarettes in those smokers unable or unwilling to stop smoking. Yet, as a physician who has seen many “fads” come and go in health care — such as vitamin E, the Atkins diet and “light” cigarettes — I would like to simply advise caution while we assess the benefit of e-cigarettes. Also, as a public health professional, I am obligated to consider the broader impact of e-cigarettes on our society.

What do we know?

E-cigarette vapor is a heated solution that often contains nicotine, along with other chemicals, such as propylene glycol and flavorings. It has been shown to contain other chemicals, such as heavy metals and formaldehyde, as well as low levels of carcinogens. However, this vapor contains no combusted tobacco smoke, and the levels of toxins are hundreds of times lower than found in cigarette smoke;

E-cigarettes are produced by numerous companies with no FDA oversight. Therefore, at the present time, there is no standardization as to what is contained in e-cigarette liquid or how much nicotine is actually delivered;

E-cigarette liquid is sold in many flavors that cannot be argued will appeal to young people, including “gummy bear,” “hot fudge sundae,” and “apple jacks – ‘like the cereal’”; and

Many smokers do not exclusively switch to e-cigarettes, but instead “dual use” e-cigarettes with their tobacco cigarettes, the harm of which is unknown.

There are experts in the field who call for widespread dissemination of e-cigarettes as a panacea for the tobacco epidemic. But these calls are based partially on anecdotal evidence and tobacco industry marketing. Do we want to run head-first in recommending a potentially beneficial product without actually taking just a bit of time to determine its actual safety and efficacy? What is the harm in gathering scientific evidence of a product that contains even low levels of nicotine and toxins? Why are we in such a rush to promote a product that clearly appeals to children whose brains are most susceptible to nicotine’s effects? Do these tobacco companies really want children as their consumers by selling cotton candy-flavored vapor liquid? What is the public health benefit of that?

I am certainly open to the possibility of considering e-cigarettes for patients with cancer who are unable or unwilling to stop smoking. As a scientist, all I ask for is proof. Some people see FDA regulation as “death” for e-cigarettes. I believe that if we are going to recommend a product as less harmful, shouldn’t we confirm that it truly is less harmful, keeping in mind that “less harmful” is not the same as safe? Show me that e-cigarettes are effective for cessation in well-designed studies, as we would want to see for any treatment. Show me that e-cigarettes will not lead children who would not otherwise take up smoking to become addicted to nicotine. Then, I will feel confident in recommending them to my patients.


Michael B. Steinberg, MD, MPH, is an associate professor of medicine at Rutgers Robert Wood Johnson Medical School, director of the Rutgers Tobacco Dependence Program and a HemOnc Today Editorial Board member. He can be reached at Rutgers Robert Wood Johnson Medical School, 125 Patterson St., New Brunswick, NJ 08901; email: steinbmb@rwjms.rutgers.edu. Disclosure: Steinberg reports consultant roles with pharmaceutical companies that have developed tobacco-dependence treatments, but he reports no funding from any tobacco or e-cigarette company.

Smoking cigarettes has long been established as the leading cause of preventable death in the United States.

The rapid growth in marketing and popularity of electronic cigarettes — which offer an alternative nicotine-delivery option to traditional, combustible tobacco products — has prompted a global public health debate.

E-cigarettes have been considered a less toxic alternative to combustible tobacco, and supporters have touted the devices as possible smoking cessation aids.

However, several medical societies — including ASCO and the American Association for Cancer Research (AACR) — have called for the regulation of e-cigarettes and other electronic nicotine delivery systems, emphasizing the need for additional research into their potential long-term adverse health effects. Further, studies have shown children can easily access the devices, prompting fears that they may serve as a gateway drug for nicotine addiction and lead to subsequent use of other tobacco products.

Evidence-based smoking cessation strategies should be preferred over the use of e-cigarettes, according to Matthew Steliga, MD, a thoracic oncologist in the department of surgery at the University of Arkansas for Medical Sciences.

Evidence-based smoking cessation strategies should be preferred over the use of e-cigarettes, according to Matthew Steliga, MD, a thoracic oncologist in the department of surgery at the University of Arkansas for Medical Sciences. “When a patient [asks about e-cigarettes], they are looking for acceptance and permission from the physician,” he said. “I don’t provide that. I tell them, ‘I don’t think it’s going to make you better. It sounds to me like you need help quitting.’”

Source: Photo by University of Arkansas for Medical Sciences

“I don’t see e-cigarettes as … making us healthy in any way,” Matthew Steliga, MD, a thoracic oncologist in the department of surgery at the University of Arkansas for Medical Sciences, told HemOnc Today. “This is not a product that is being pushed out by academia. It is a product being pushed out by industry. There are some countries where e-cigarettes are not permitted at all.”

The FDA proposed a new “deeming rule” in April 2014 that would allow it to regulate tobacco-related products — such as e-cigarettes, cigars, pipe tobacco, dissolvable products that are not “smokeless tobacco,” gels and waterpipe tobacco — under the Federal Food, Drug and Cosmetic Act.

The FDA told HemOnc Today it had received more than 135,000 public comments on the deeming proposal as of March. The final rule is expected in June.

“You hear statements about electronic cigarettes claiming that they may help,” Steliga said. “If that’s truly the case, then they should be considered a drug-delivery device and should be regulated by the FDA. So far, [e-cigarettes] have fallen through a lot of loopholes in regulation, oversight, distribution, sales and taxation.”

HemOnc Today spoke with oncologists and experts in tobacco-related cancers about whether e-cigarettes offer any health benefits to current smokers compared with traditional cigarettes, how a lack of data has influenced the public perception of the devices and how strictly they should be regulated by the FDA.

Gateway for addiction

Without FDA regulation of e-cigarettes, their popularity — and availability — continues to skyrocket.

E-cigarettes — or electronic nicotine delivery systems (ENDS) — were first introduced to the U.S. market in the early 2000s. At that time, they were distributed over the Internet through smaller, independent companies.

There are now more than 460 ENDS brands available online in more than 7,700 flavors, according to a joint policy statement from AACR and ASCO co-published in March in Journal of Clinical Oncology and Clinical Cancer Research.

Advertising for e-cigarettes also has exploded. Advertising sales for e-cigarettes increased from $5.6 million in 2010 to $82.1 million in 2013, according to a 2014 report published by Legacy, a public trust organization created as part of the Tobacco Master Settlement Agreement to study and educate the public about the impact of tobacco.

This increase in spending may be attributed to the fact that many e-cigarette brands are now owned by major tobacco companies, experts said. In addition, the use of advertising — as well as the variety of available flavoring options — suggest e-cigarette marketing is increasingly directed toward a younger audience.

“Chocolate, strawberry, bubble gum, gummy bear-flavored nicotine fluid?” Steliga said. “Who are you marketing that toward? By candying it up, not only does it appeal to younger people, but it also makes it seem safer and distances it from tobacco. That is a big, big worry.”

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A study by Bunnell and colleagues, published in August 2014 in Nicotine and Tobacco Research, showed the number of middle school-aged to high school-aged youth who had never smoked a cigarette but who used an e-cigarette increased threefold from 79,000 in 2011 to 263,000 in 2013. A study by Arrazola and colleagues, published in April in Morbidity and Mortality Weekly Report, indicated current use of e-cigarettes among middle and high school students tripled — from 4.5% to 13.4% — from 2013 to 2014.

Eric J. Jacobs, PhD

Eric J. Jacobs

“Regulation of e-cigarettes is urgently needed; a nicotine addiction warning is not enough,” Eric J. Jacobs, PhD, strategic director of pharmacoepidemiology for the American Cancer Society, told HemOnc Today. “One important recommendation from [the AACR/ASCO policy statement] is restricting youth-oriented marketing of e-cigarettes, which would include [regulation of] strategies such as use of cartoon characters in advertising, sponsorship of rock concerts, and distribution of hats and T-shirts with e-cigarette brand logos. Another strategy is to require Internet and mail-order companies to verify age and not sell to minors.”

Williams and colleagues evaluated the ease with which minors could purchase e-cigarettes online. Results — published in March in JAMA Pediatrics — showed 11 nonsmoking minors aged 14 to 17 years made supervised e-cigarette purchase attempts from 98 vendors between February and June 2014. Researchers reported 76.5% of these orders were delivered successfully, with no attempts to verify the purchasers’ ages at the time of delivery.

“The most worrisome thing is that it renormalizes smoking,” Steliga said. “This could try to make smoking more acceptable, especially for youth who are nonsmokers. When you take your first drag on a cigarette as a youth, it’s probably going to make you cough and it isn’t a pleasant experience. I worry that any youth who initiate their addiction by these ENDS are being drawn in by novelty and technology. Once introduced to nicotine, cigarettes could follow.”

Bunnell and colleagues demonstrated that a higher percentage of youth who had smoked e-cigarettes than never users intended to smoke conventional cigarettes (43.9% vs. 21.5%). Overall, e-cigarette users were significantly more likely to have smoking intentions than never users (adjusted OR = 1.7; 95% CI, 1.24-2.32).

Jamie S. Ostroff, PhD

Jamie S. Ostroff

“The most important regulations have to come about for youth use,” Jamie S. Ostroff, PhD, chief of behavioral sciences service and director of the tobacco treatment program at Memorial Sloan Kettering Cancer Center, told HemOnc Today. “The current lack of regulation of e-cigarettes allows there to be a resurgence of the advertisements that were promulgated in the 1960s and 1970s. Anyone who is even a casual historian of tobacco control knows that those ads were highly effective and highly resourced. There are a lot of questions about the safety and potential benefits of e-cigarettes, but FDA regulation guided by a clear understanding of youth attitudes and use patterns is perhaps the most critical need for prevention of tobacco-related morbidity and mortality.”

Need for regulation

When the FDA’s “deeming rule” is finalized, the agency will be able to immediately begin regulation of e-cigarettes.

“Public health-based regulation of these products can help reduce the death and disease toll from tobacco use, and help FDA protect public health by requiring the review of new tobacco products and health-related claims for regulated tobacco products in today’s rapidly evolving marketplace,” the agency stated in an email to HemOnc Today.

The FDA’s draft proposal would require manufactures of e-cigarettes to register their products with the FDA and report product and ingredient listings; adhere to minimum age and identification restrictions to prevent sales to underage youth; include health warning labels; and only market new tobacco products after FDA review. The regulation also would ban the distribution of free samples, vending machine sales in facilities that admit youth, and use of reduced-risk claims such as “light” or “mild” unless the manufacturer provides valid scientific data to support such claims and is granted an FDA market authorization.

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Graham Warren, MD, PhD

Graham Warren

“I think that’s a good start,” Graham Warren, MD, PhD, vice chairman for research in radiation oncology at Medical University of South Carolina and chair of ASCO’s Tobacco Cessation and Control Subcommittee, which helped develop the AACR/ASCO joint statement on e-cigarettes, told HemOnc Today. “The problem is, we don’t know what the health effects of e-cigarettes are. It’s very difficult to think that they are worse than smoking, but we don’t have data on that yet. At the same time, they are going to be more harmful than not using e-cigarettes at all, so there’s going to be some adverse health effects associated with them we need to figure out.”

The fact that there are so many different types of e-cigarettes may complicate regulation and data collection, Warren said.

“One of the biggest problems we have to contend with is that there are hundreds of different e-cigarette products with thousands of variations — even though there are not as many compounds as are in cigarette smoke — and the individual constituents of e-cigarette fluid can change, as well as how they are heated, vaporized and absorbed,” Warren said. “Due to the complexity of constituents in e-cigarettes, it is very difficult to try to say, ‘We know they are all going to behave the same way.’ We may find that one change in the chemical constituents in the liquid, heating element or the delivery system can dramatically alter behavior, absorption or health effects. That’s going to be a challenge for the FDA to accurately assess and regulate e-cigarettes.”

The FDA may not strictly regulate e-cigarettes until more research is available, thereby allowing for evidence-based reform, experts said.

Bruce E. Johnson, MD, professor of medicine in the department of adult oncology at Dana-Farber Cancer Institute and Harvard Medical School, told HemOnc Today that the FDA should treat e-cigarettes no differently than combustible cigarettes.

Bruce E. Johnson, MD

Bruce E. Johnson

“They should be regulated the same way as combustible cigarettes, although we’ve never been able to muster the will to regulate cigarette sales the way I think we should in the United States,” Johnson said. “With electronic cigarettes, we have a chance at a fresh start. But e-cigarettes are a two-headed monster. If electronic cigarettes are an effective means to help people stop smoking, they might be useful to people who are addicted to cigarettes. But, they are the third most common form of nicotine sources for people who have not graduated from high school after cigarettes and cigars. If they are more easily accessible than tobacco products, it has potential to start nicotine addiction in the younger population. So, when thinking about regulating them, you have to weigh both factors and populations.”

The FDA said it plans to weigh the risks and benefits, and then will address concerns raised during the comment period within its final rule.

“FDA knows that, though all tobacco products are potentially harmful and potentially addictive, different categories of tobacco products may have the potential for varying effects on public health,” the FDA told HemOnc Today in a statement. “Regulating these products allows FDA to properly understand the relative impacts of the product categories, and to evaluate how individual products in each category may affect public health.”

Benefits vs. harms

Overall, the regulation of e-cigarettes may prove challenging due to a lack of data.

Along with the need to better understand the potential harms of e-cigarettes, any claims that e-cigarettes are effective smoking cessation aids would be premature, Ostroff said.

“There are different types of adult users,” Ostroff said. “There are some people who are finding that e-cigarettes are an acceptable replacement for smoking and are quitting combustible cigarettes altogether. There are others who are finding that e-cigarettes are partially acceptable, and they are dual smoking and successfully reducing their amount of combustible smoking. Then there are those who are dual using but aren’t changing their combustible smoking habits.”

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A population-based study by Al-Delaimy and colleagues, published in April in American Journal of Public Health, did not support the use of e-cigarettes as smoking cessation aids. Results from 1,000 California smokers indicated those who also used e-cigarettes were 49% less likely to decrease traditional cigarette use and 59% less likely to quit smoking compared with smokers who did not use e-cigarettes.

Data also are needed to compare e-cigarettes with other smoking cessation aids.

“They haven’t been around nearly long enough to compare to nicotine replacements and antidepressants in treating nicotine addiction,” Johnson said. “The potential health implications of electronic cigarettes — namely their safety — haven’t been defined. Inhaling nicotine in a heated vapor is probably not good for you. It took almost 40 years since the introduction of mass-produced cigarettes before a link to lung cancer was made.”

Johnson cited multiple articles published in PLoS One in the last year that have presented preliminary evidence of inflammation and damage of the lungs associated with materials in e-cigarettes. One such study, conducted by Sussan and colleagues, used a mouse model to demonstrate that e-cigarettes impaired pulmonary antibacterial and antiviral defenses.

Yet, there still could be a public health benefit.

At the 2015 American Association for the Advancement of Sciences meeting, a presentation titled “E-Cigarettes: What’s the Real Medical Innovation Breakthrough?” by Kevin Bridgman, MD, chief medical officer of Nicovations — a subsidiary of British American Tobacco — suggested e-cigarettes could offer the same progressive step down from smoking as nicotine patches or gum, but with a greater appeal to smokers because of the similarity to traditional smoking.

Bridgman referenced a yet-to-be-published study conducted by Neilson and colleagues that used the EpiAirway (MatTek) model, a highly differentiated in vitro human epithelial tissue culture. In the study, cigarette smoke reduced cell viability to 12% at 6 hours, whereas e-cigarettes were associated with results similar to untreated air controls.

“There is growing consensus among public health professionals that e-cigarettes are significantly less risky than conventional cigarettes,” Bridgman said in a press release. “However, we believe that, in order to realize their full potential, e-cigarettes should be regulated to ensure appropriate quality and safety standards, whilst also allowing sufficiently wide retail availability, appropriate lifestyle positioning and flexibility for the rapid introduction of product innovation. This would provide greater confidence without stifling innovation while enabling these products to compete effectively with cigarettes.”

Still, e-cigarettes have not been marketed as cessation aids, perhaps because they are developed by the tobacco industry, experts said.

“The long-term health risks of e-cigarette use are not known,” Jacobs said. “Most researchers agree that because combustible cigarettes are so lethal, switching to exclusive use of e-cigarettes would likely be helpful. However, many people use both e-cigs and combustible cigarettes. One concern is that some combustible cigarette smokers may be less likely to quit if they can maintain their nicotine addiction by using e-cigs at work or in other places where smoking combustibles is banned.”

Oncologic concerns

The AACR/ASCO policy statement encouraged health care providers to direct patients who use tobacco products to choose evidence-based cessation tools until the long-term safety of e-cigarettes is established.

However, patients may ask their oncologists about e-cigarettes before these data become available.

“I get asked that question all the time and I tell patients, unfortunately, I can’t say with any certainty if e-cigarettes are safer, equivalent or worse,” Warren said.

In this scenario, rather than waiting years for mature trial data, it may be warranted to rely on information from preclinical studies, Johnson said.

“This is the one time where animal models can be applicable to the human condition, because we have decades of information about what happens to humans after long-term exposure to cigarette smoke and how it compares to animal models,” Johnson said. “I think we will be able to tell the relative impact [of e-cigarettes] on people’s lungs by vaping in animals in a shorter period of time.”

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Ostroff, who co-authored the AACR/ASCO policy statement, concluded that she and her colleagues should work with patients with cancer to develop acceptable, evidence-based tobacco cessation treatment plans. Still, physicians cannot ignore that many patients are interested in using e-cigarettes as part of their efforts to quit smoking, she said.

“We have the responsibility to provide education and counseling about potential risks and benefits of e-cigarettes,” Ostroff said. “Smokers who want to quit want to be successful, and the available evidence supports use of behavioral counseling and cessation medications (eg, nicotine replacement therapies, varenicline [Chantix, Pfizer] and bupropion) that have undergone rigorous testing.”

Steliga, on the other hand, would rather his patients not consider e-cigarettes. Instead, he favors evidence-based strategies.

“There’s all kinds of people who smoke who want to quit,” he said. “If you survey people and ask them if they’d like to quit, more than half of them would say yes. However, nicotine is one of the most addictive substances known to man. Nicotine fluid is highly toxic. … We have secondhand smoke data, but we don’t have secondhand vapor data. Still, if it’s foreign material you are sucking into your lungs, it probably is not making your lungs better.”

Evidence-based smoking cessation methods do exist, Steliga said.

“When a patient [asks about e-cigarettes], they are looking for acceptance and permission from the physician,” he said. “I don’t provide that. I tell them, ‘I don’t think it’s going to make you better. It sounds to me like you need help quitting.’ I try to get them to meet with a counselor first who has expertise in tobacco cessation. In our cancer center, we have put a tobacco treatment specialist in the clinic who is there with me when I see the patient.”

Rather than help smokers quit, e-cigarettes could be a setback, diminishing some of the progress made in the effort to reduce smoking prevalence, Steliga said.

“There’s so much we don’t know and so much harm that can still be done [with e-cigarettes],” he said. “We are seeing a drop in lung cancer death — not because of some magic bullet cure, but because of a drop in lung cancer incidence. That’s happening because smoking rates are decreasing. That’s important. We need to get people to quit smoking using evidence-based strategies. There are too many unknowns about the long-term outcome of e-cigarettes.” – by Anthony SanFilippo

References:

Al-Delaimy W, et al. Am J Public Health. 2015;doi:10.2105/AJPH.2014.302482.

Arrazola RA, et al. MMWR. 2015;64:381-385.

Brandon TH, et al. J Clin Oncol. 2015; doi:10.1200/JCO.2014.59.4465.

Bridgeman K. E-cigarettes: Public health threat or opportunity? Presented at: American Association for the Advancement of Science meeting; Feb. 12-16, 2015; San Jose, Calif.

Bunnell RE, et al. Nicotine Tob Res. 2014;doi:10.1093/ntr/ntu166.

Hughes K, et al. BMC Public Health. 2015;doi:10.1186/s12889-015-1618-4.

Sussan TE, et al. PLoS One. 2015;doi: 10.1371/journal.pone.0116861.

Williams RS, et al. JAMA Pediatr. 2015;doi:10.1001/jamapediatrics.2015.63.

For more information:

Eric J. Jacobs, PhD, can be reached at the American Cancer Society, 250 Williams St., Atlanta, GA 30303; email: eric.jacobs@cancer.org.

Bruce E. Johnson, MD, can be reached at Dana Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215; email bejohnson@partners.org.

Jamie S. Ostroff, PhD, can be reached at Memorial Sloan Kettering Cancer Center, 641 Lexington Ave., 7th Floor, New York, NY 10022; email: ostroffj@mskcc.org.

Matthew Steliga, MD, can be reached at the University of Arkansas for Medical Sciences, Winthrop P. Rockerfeller Cancer Center, 4301 West Markham St., #713, Little Rock, AR 72205; email: masteliga@uams.edu.

Graham Warren, MD, PhD, can be reached at the Medical University of South Carolina, 165 Cannon St., #503, Charleston, SC 29403; email: warrengw@musc.edu.

Disclosure: The researchers report no relevant financial disclosures.

 

POINTCOUNTER

Are e-cigarettes a viable smoking cessation tool for patients with cancer?

POINT

E-cigarettes are indeed a viable alternative for patients with cancer who are smokers and who are unable to quit using other methods.

Michael B. Siegel, MD, MPH

Michael B. Siegel

There are several clinical trials that demonstrate that e-cigarettes are at least as effective as the nicotine patch for smoking cessation. With new innovations that have entered the marketplace recently, it is likely that the effectiveness of e-cigarettes has increased substantially from these early trials.

The advantage of e-cigarettes is that — unlike the nicotine patch and other cessation drugs — they address both the pharmacologic and behavioral aspects of smoking addiction. Nicotine replacement therapy only addresses the pharmacologic aspect of addiction — that is, the need for nicotine. But we know that smoking addiction involves a lot more than just the nicotine.

There are the hand motions, the physical sensation of the cigarette, the oral sensation, the throat hit, the social aspects of smoking, the associations of smoking with other behaviors — all of these contribute to making smoking one of the most addictive behaviors. The e-cigarette is really the first smoking cessation product that can address these behavioral and social aspects of smoking addiction, and it is for this reason that the product is so popular.

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The tremendous growth in the sale of these products and the projections that these products may substantially replace cigarettes in the market are a testament to the fact that these products really work. There are thousands of smokers who have successfully quit by using e-cigarettes, and many others who have cut down substantially on the amount they smoke and greatly improved their health as a result. I don’t see any reason these alternatives should not be available to smokers, and especially to patients with cancer who really need to do something to end their smoking addiction as urgently as possible.

It would actually be tragic to withhold or otherwise discourage these patients from trying a product that could literally save their lives.

Michael B. Siegel, MD, MPH, is a professor in the department of community health sciences at Boston University School of Public Health. He can be reached at Boston University School of Public Health, 801 Massachusetts Ave., Crosstown Center, Boston, MA 02118; email: mbsiegel@bu.edu. Disclosure: Siegel reports no relevant financial disclosures.

COUNTER

More data are needed before we should recommend e-cigarettes to our patients.

Michael Steinberg

Michael B. Steinberg

As someone who cares for patients with cancer, I can appreciate the appeal of e-cigarettes in those smokers unable or unwilling to stop smoking. Yet, as a physician who has seen many “fads” come and go in health care — such as vitamin E, the Atkins diet and “light” cigarettes — I would like to simply advise caution while we assess the benefit of e-cigarettes. Also, as a public health professional, I am obligated to consider the broader impact of e-cigarettes on our society.

What do we know?

E-cigarette vapor is a heated solution that often contains nicotine, along with other chemicals, such as propylene glycol and flavorings. It has been shown to contain other chemicals, such as heavy metals and formaldehyde, as well as low levels of carcinogens. However, this vapor contains no combusted tobacco smoke, and the levels of toxins are hundreds of times lower than found in cigarette smoke;

E-cigarettes are produced by numerous companies with no FDA oversight. Therefore, at the present time, there is no standardization as to what is contained in e-cigarette liquid or how much nicotine is actually delivered;

E-cigarette liquid is sold in many flavors that cannot be argued will appeal to young people, including “gummy bear,” “hot fudge sundae,” and “apple jacks – ‘like the cereal’”; and

Many smokers do not exclusively switch to e-cigarettes, but instead “dual use” e-cigarettes with their tobacco cigarettes, the harm of which is unknown.

There are experts in the field who call for widespread dissemination of e-cigarettes as a panacea for the tobacco epidemic. But these calls are based partially on anecdotal evidence and tobacco industry marketing. Do we want to run head-first in recommending a potentially beneficial product without actually taking just a bit of time to determine its actual safety and efficacy? What is the harm in gathering scientific evidence of a product that contains even low levels of nicotine and toxins? Why are we in such a rush to promote a product that clearly appeals to children whose brains are most susceptible to nicotine’s effects? Do these tobacco companies really want children as their consumers by selling cotton candy-flavored vapor liquid? What is the public health benefit of that?

I am certainly open to the possibility of considering e-cigarettes for patients with cancer who are unable or unwilling to stop smoking. As a scientist, all I ask for is proof. Some people see FDA regulation as “death” for e-cigarettes. I believe that if we are going to recommend a product as less harmful, shouldn’t we confirm that it truly is less harmful, keeping in mind that “less harmful” is not the same as safe? Show me that e-cigarettes are effective for cessation in well-designed studies, as we would want to see for any treatment. Show me that e-cigarettes will not lead children who would not otherwise take up smoking to become addicted to nicotine. Then, I will feel confident in recommending them to my patients.


Michael B. Steinberg, MD, MPH, is an associate professor of medicine at Rutgers Robert Wood Johnson Medical School, director of the Rutgers Tobacco Dependence Program and a HemOnc Today Editorial Board member. He can be reached at Rutgers Robert Wood Johnson Medical School, 125 Patterson St., New Brunswick, NJ 08901; email: steinbmb@rwjms.rutgers.edu. Disclosure: Steinberg reports consultant roles with pharmaceutical companies that have developed tobacco-dependence treatments, but he reports no funding from any tobacco or e-cigarette company.