Abeloff's Clinical Oncology, 4th Edition

Part I – Science of Clinical Oncology

Section D – Preventing and Treating Cancer

Chapter 27 – Nicotine Dependence: Current Treatments and Future Directions

Caryn Lerman,Robert A. Schnoll,
Freda Patterson

SUMMARY OF KEY POINTS

Prevalence and Impact

  

   

Approximately one in five American adults are current smokers.

  

   

Smoking accounts for one third of all cancer deaths.

Current Treatments

  

   

Nonpharmacologic treatments include behavioral counseling (e.g., identifying triggers, managing withdrawal), quit lines, and self-help material (e.g., booklets and video).

  

   

These approaches are popular but yield relatively low quit rates.

  

   

The FDA-approved pharmacologic treatments, including nicotine replacement therapies (NRTs; i.e., transdermal patch, gum, nasal spray, inhaler, and lozenge) and bupropion, have been shown to double smoking cessation rates as compared to placebo.

  

   

Varenicline, a new FDA-approved medication, has efficacy superior to that of NRTs and bupropion.

Smoking among Cancer Patients

  

   

Approximately one half of cancer patients continue to smoke after diagnosis, even though tobacco use can heighten risk for a second primary tumor and diminished quality of life.

  

   

Few studies have examined predictors of continued smoking among cancer patients, and even fewer trials of smoking cessation treatments have been conducted among cancer patients.

Barriers to Cessation Treatment in Clinical Oncology

  

   

Physicians have limited time to address smoking among cancer patients, and patients may possess unique psychological characteristics that undermine their ability to quit smoking.

  

   

Systems-level changes and tailored treatment approaches might be needed to lower the rate of persistent tobacco use among cancer patients.

Future Directions

  

   

Research is needed to identify new medications for nicotine dependence and to evaluate these approaches with cancer patients.

  

   

Pharmacogenetics research might help to guide the tailoring of treatments for subgroups of smokers to enhance efficacy and reduce toxicity.

INTRODUCTION

Despite several decades of research to identify new approaches to treat nicotine dependence, about 21% of adults in the United States are regular smokers, suggesting that the Healthy People 2010 objective of reducing U.S. adult smoking to 12% will not be attained.[1] Each year, cigarette smoking causes more than 400,000 premature deaths in the United States and 4.2 million premature deaths around the world from cancer, cardiovascular and respiratory diseases, and perinatal conditions.[1] Tobacco use accounts for at least 30% of all cancer deaths in the United States, and smoking has been causally linked to lung, head and neck, esophageal, pancreatic, bladder, kidney, cervical, endometrial, and gastric cancer and acute myeloid leukemia.[2] Furthermore, persistent tobacco use among cancer patients increases risk for disease recurrence, second-primary tumors, adverse reactions to therapy, diminished quality of life, and reduced survival.[3] Despite these data, 46% to 75% of cancer patients report smoking at the time of their diagnosis, and close to one half of these patients continue to smoke during and following medical treatment.[4]

This chapter provides an overview of the state of the art in smoking cessation treatment. First, we provide an overview of nonpharmacologic and pharmacologic treatments for nicotine dependence and highlights factors that affect treatment response. Second, we review the epidemiology of tobacco use among cancer patients, studies of predictors of tobacco use in this population, and studies of smoking cessation interventions with cancer patients. Third, physician and health care system and patient barriers to smoking cessation are discussed, and methods for overcoming these barriers are suggested. Fourth, we briefly review public policy initiatives that are used to reduce cigarette consumption, such as advertising bans, taxes on cigarettes, and smoke-free policies. We conclude with a brief discussion of potential new pharmacologic treatments for nicotine dependence as well as novel treatment approaches, including pharmacogenetics research. Some material in this chapter was adapted from an earlier publication.[5]

CURRENT TREATMENTS FOR NICOTINE DEPENDENCE

There are two general classes of treatments for nicotine dependence: nonpharmacologic and pharmacologic ( Fig. 27-1 ). In the following sections, we describe these treatment approaches, with an emphasis on efficacy data and moderators of treatment response.

 
 

Figure 27-1  Overview of FDA-approved available smoking cessation treatments.

 

 

Nonpharmacologic Treatments

Nonpharmacologic smoking cessation treatments such as self-help interventions and behavioral counseling are the preferred mode of treatment for most smokers.[6] These include informational booklets, audiotapes and videotapes or DVDs, and Internet-based programs that are designed to help smokers quit on their own.[7] Behavioral therapies include elements of nicotine fading, quit date contracting, management of smoking triggers, and relaxation techniques delivered either in a group or individual context.[7] The efficacy of these approaches is reviewed in the following discussion.

Self-Help Materials

Self-help smoking cessation interventions are reported to produce quit rates in the range of 4% to 11%[8] and are significantly more effective than no intervention at all.[9] Multimodal, more intense interventions are more effective than are single-modal, less intense interventions, while tailoring materials to individual characteristics has also been demonstrated to be a potentially effective strategy to enhance self-help quit rates. For example, in a sample of 300 treatment-seeking smokers, those who received computer-generated, tailored mailed feedback had significantly higher quit rates 1 year following the target quit date than did those who received standard advice (25% versus 10%, respectively).[10] The Internet has emerged as another vehicle through which self-help smoking cessation interventions can be delivered, with over 10 million Internet users in the United States searching for quit smoking information in 2004 and an estimated 75% self-reporting as current smokers.[11] Although only a small number of studies have evaluated the efficacy of Internet-based cessation approaches, one study did report that, at 3 months after the target quit date, a tailored, Internet-based cessation intervention produced a quit rate of 24% versus 5% in the control condition (P < 0.05).[12] These data are consistent with other preliminary work showing the efficacy of Internet-based cessation interventions;[13] however, more controlled trials in this area are needed before this approach can be considered a primary mode for the delivery of nicotine dependence treatment programs.

Behavioral Therapies

Behavioral therapies for smoking cessation include elements of nicotine fading, quit date contracting, management of smoking triggers, and relaxation techniques and have been reported to produce quit rates of 7% to 20%. [14] [15] In one 3-month cognitive-behavioral smoking cessation program that provided participants with instruction and guidance on nicotine fading, quit date contracting, relaxation strategies, trigger management, and relapse prevention, end-of-treatment quit rates of 17.2% were reported as compared to 5.6% in the educational control condition.[16] No significant differences in individual versus group-based programs have been found.[17]

Telephone-based cessation counseling has become increasingly available in the United States, with 36 states providing quit lines for treatment-seeking smokers.[18] The efficacy of proactive telephone counseling (i.e., the cessation counselor initiates the call) has been well demonstrated,[19] producing 12-month quit rates in the range of 7% to 10%, the higher quit rates being achieved by recipients of more frequent calls. [20] [21] Reactive telephone counseling (i.e., the patient initiates contact) such as that provided by state quit lines and hot lines has also been shown to be efficacious. [19] [22] However, there is limited literature on the efficacy of statewide smoking cessation hot lines at this time.

Pharmacologic Treatments

FDA-Approved Nicotine Replacement Therapies

Five nicotine-replacement therapies (NRTs) have been approved by the U.S. Food and Drug Administration (FDA) for treating nicotine dependence: transdermal patch, gum, nasal spray, inhaler, and lozenge ( Table 27-1 ); a sixth NRT, the sublingual tablet, is used only in Europe.[23] NRTs treat nicotine dependence by (1) ameliorating withdrawal symptoms that characterize initial physical and psychological reactions to cessation, such as irritability, restlessness, depressed mood, and poor concentration; (2) reducing the experience of nicotine craving on cessation and limiting possible weight gain (for gum and the patch); and (3) providing a safer way to experience the neurobiological and psychophysiologic effects of nicotine. NRTs are tolerable and safe and almost double quit rates compared to placebo (pooled OR = 1.77, 95% CI: 1.66 to 1.88).[24] Indirect[24] and head-to-head[25] comparisons indicate comparable efficacy between NRTs. However, NRTs do not provide nicotine as effectively as cigarettes do or adequately mimic the behavioral ritual of smoking. Furthermore, at best, only one quarter to one third of smokers who use NRTs to quit smoking will remain successfully abstinent 6 months following treatment completion. [24] [25]


Table 27-1   -- FDA-Approved Medications for Tobacco Dependence

Medication

Recommended Duration and Dose[*]

Estimated Quit Rate[†](95% CI) Number of Studies

Advantages

Disadvantages

Cost

Nicotine gum

Up to 12 weeks; 2 mg (for those who smoke <25 cigarettes/day; 4 mg (for those who smoke ≥25 cigarettes/day

17.4%

Treat oral behavioral ritual and cue-elicited craving; prevent weight gain

Adverse side effects and poor compliance

$4.00 to $5.00/day

 

 

(17% to 18%)

 

 

 

 

 

52 trials[24]

 

 

 

Nicotine patch

Up to 10 weeks; dose duration varies by cigarettes/day

13.7%

Better compliance and nicotine replacement; few side effects

Does not treat cue-elicited craving

$2.50/day

 

 

(13% to 15%)

 

 

 

 

 

37 trials[24]

 

 

 

Nicotine spray

Up to 6 months; 8 to 40 sprays/day

24%

Nicotine is rapidly absorbed; treat cue-elicited craving

Unpleasant side effects and poor compliance

$5.00 to $15.00/day

 

 

(20% to 28%)

 

 

 

 

 

4 trials[24]

 

 

 

Nicotine inhaler

Up to 6 months; 6 to 16 cartridges/day

17%

Treat oral behavioral ritual and cue-elicited craving

Unpleasant side effects and poor compliance

$7.00 to $18.50/day

 

 

(14% to 21%)

 

 

 

 

 

4 trials[24]

 

 

 

Nicotine lozenge

Up to 12 weeks; 2 mg (for those who smoke their first cigarette more than 30 minutes after waking) and 4 mg (for those who smoke their first cigarette within 30 minutes of waking)

17%

Good nicotine replacement; treats oral behavioral ritual and treats cue-elicited craving; few side effects

Compliance is unknown

$3.00 to

 

 

(15% to 20%)

 

 

$4.00/day

 

 

4 trials[24]

 

 

 

Bupropion

Up to 12 weeks; 300 mg/day; 150 mg per day for 3 days, then 300 mg/day from day 4 to end of treatment

19%

Good side effect profile; low abuse liability; prevent weight gain

Relatively more costly

$4.00 to $5.00 (300 mg)

 

 

(Range: 4% to 43%)

 

 

 

 

 

2 trials[28]

 

 

 

 

 

31 trials[40]

 

 

 

Varenicline

Up to 12 weeks; 2 mg/day; 0.5 mg for days 1 to 3, 0.5 mg twice daily for 4 days, and 1 mg twice daily from day 8 to end of treatment

30%

Well-tolerated; reduces withdrawal and reinforcing effects of nicotine

Limited data

Unknown

 

 

2 trials [54] [55]

 

 

 

*

Recommendations are taken from the manufacturer of the agent and/or from Fiore[28].

6-month or greater point-prevalence quit rates, biochemically verified.

 

Identifying factors related to NRT responsiveness, including characteristics of the NRT as well as characteristics of the smoker, may lead to methods for enhancing NRT efficacy. One study found no difference in quit rates when NRT was used for a longer duration;[26] however, large-scale placebo-controlled trials testing the effects of extended NRT use are needed. Other studies have examined the efficacy of higher-dose NRT; however, findings thus far have not been supportive.[27] Meta-analytic reviews of studies that evaluated combination NRT therapy versus a single NRT show that combination therapy is somewhat more effective (OR = 1.42, 95% CI: 1.14 to 1.76[24] versus OR = 1.9, 95% CI: 1.3 to 2.6).[28] However, studies in this area have not been entirely consistent.[29] More recently, one study found that using the patch for 2 weeks prior to quitting doubled the likelihood of 4-week continuous abstinence, compared to standard patch use.[30] Finally, since NRT efficacy may be related to how rapidly nicotine is delivered into the central nervous system,[31] studies have begun to investigate rapid-release NRT. Niaura and colleagues[32] found that rapid-release nicotine gum significantly reduced postcessation cravings compared to standard nicotine gum, suggesting the need for clinical trials of rapid-release formulations of NRT.

Likewise, a range of smoker characteristics can affect response to NRTs, suggesting that the tailored use of NRT for subgroups of smokers could improve NRT efficacy.[33] The level of nicotine dependence affects response to NRT, more dependent smokers showing higher quit rates when they receive higher doses of NRTs. [34] [35] Lerman and colleagues[25] also found that smokers with low to moderate levels of dependence have higher quit rates with the patch, while those with high levels of dependence have higher quit rates with the nasal spray. Caucasian smokers and nonobese smokers also showed higher quit rates on the patch, whereas smokers from racial and ethnic minority groups and obese smokers showed higher quit rates with the nasal spray.[25] Last, gender may affect response to NRT. While early placebo-controlled trials of NRT reported lower efficacy for women than men, two meta-analyses [36] [37] indicate that NRTs have equal efficacy for women and men. However, meta-analytic studies included trials that provided only partial outcome data, omitted some relevant trials, and might have had limited statistical power to examine gender differences in light of low absolute quit rates.[38]Furthermore, another meta-analytic study found that NRT was less effective for maintaining long-term cessation for women versus men.[39]

FDA-Approved Nonnicotine Pharmacologic Treatments

Bupropion SR (Zyban) is an antidepressant that reduces the uptake of dopamine and norepinephrine (see Table 27-1 ). A meta-analysis[40] of 31 placebo-controlled trials concluded that bupropion more than doubled the likelihood of cessation compared to placebo, up to 12 months from a quit date (OR = 1.94, 95% CI: 1.72 to 2.19). The exact mechanism through which bupropion treats nicotine dependence is not fully known; however, the efficacy of this medication is mediated, in part, by reduction of dopamine and norepinephrine uptake[41] and/or nicotinic receptor antagonist effects.[42] A second mechanism may involve the drug's ability to prevent or diminish postcessation negative affect and weight gain, which are frequently cited as causes of relapse among smokers [43] [44] Nevertheless, upward of three quarters of smokers who use bupropion to quit smoking do not achieve long-term abstinence. Therefore, researchers have begun to examine factors related to bupropion response. Research in this area has assessed clinical depression and depressive symptoms as a moderator of treatment response. To date, no clinical trial has formally examined the role of depression as a moderator of bupropion efficacy by using depression a priori as a stratification variable. However, trials that conducted post hoc analysis to address this issue have not supported the hypothesis that bupropion is more effective for depressed smokers. [45] [46] [47] Researchers have also examined gender as a moderator of bupropion response. With few exceptions, placebo-controlled trials indicate comparable efficacy of bupropion for women and men. [48] [49] However, there is some indication that the use of bupropion to prevent relapse is less effective for women than for men.[50]

Varenicline (Chantix) is an a4b2 neuronal nicotinic acetylcholine receptor (nAChR) partial agonist (see Table 27-1 ). By activating a4b2 nAChRs receptors, which are expressed widely on dopamine and GABA neurons in the ventral tegmental area, varenicline attenuates nicotine's effect on dopamine release, while maintaining dopaminergic tone.[51] Varenicline's agonist function may minimize craving and withdrawal, while its antagonist properties may attenuate the reinforcing effects of nicotine, thereby reducing satisfaction from a “slip” cigarette and the likelihood of relapse. [52] [53] The recent FDA approval for varenicline was based on the results from three clinical trials. The first two trials randomized 2,052 smokers to placebo, 300 mg bupropion, or 2 mg varenicline for 12 weeks and assessed quit rates up to 1 year following the start of treatment. [54] [55] Assessment of continuous quit rates for the last 4 weeks of treatment (weeks 9 to 12) across the two trials at the end of treatment showed an advantage for varenicline (44%) compared to bupropion (30%) and placebo (18%). The continuous quit rate for varenicline at the 1-year follow-up diminished (22%), but it remained significantly better than those for bupropion (16%) or placebo (10%). In a third study,[56] smokers received open-label varenicline (1 mg b.i.d.) for 12 weeks; subjects who remained abstinent at the end of 12 weeks were randomized to 12 additional weeks of 1 mg b.i.d. varenicline or placebo. An assessment conducted 28 weeks from the end of the second 12-week treatment phase showed that extended varenicline use prevented relapse. Across all trials, adverse events and rates of discontinuation were similar for placebo and varenicline, indicating that varenicline is well tolerated.

Since varenicline is a relatively new treatment for nicotine dependence, little is known about moderators of treatment response. Gonzales and colleagues reported gender differences in therapeutic response.[54] Biochemically confirmed continuous abstinence rates for weeks 9 to 12 were equivalent for men and women (43% versus 46%, respectively). Furthermore, there were no gender differences in 12-month quit rates in varenicline-treated participants in a pooled analysis of data from the three trials.[57]

TOBACCO USE IN THE ONCOLOGIC SETTING

While numerous studies have documented the rate of smoking among cancer patients, few studies have examined predictors of smoking by cancer patients and cessation interventions for this population. Accumulating data show that persistent tobacco use following a diagnosis can increase the risk for a second primary tumor, shorten survival duration, exacerbate treatment-related side effects, and diminish quality of life.[3] These findings have sparked greater interest in addressing tobacco use in this population. In the following sections, we provide an overview of the research that has been conducted to date concerning tobacco use among cancer patients.

Smoking Rates among Cancer Patients

Given the etiologic role of smoking in cancer, it is not surprising that rates of tobacco use among certain subgroups of cancer patients exceed rates in the general population. The vast majority of studies in this area have concentrated on lung cancer patients and head and neck cancer patients.[4] However, studies have also evaluated smoking among cervical[58] and bladder[59] cancer patients and among survivors of childhood cancers.[60] Among head and neck cancer patients, prevalence rates of continued smoking range from 25% to 90%. [61] [62] [63] [64] [65] [66] Among lung cancer patients, prevalence rates of continued smoking range from 29% to 63%. [67] [68] Variability in rates is likely due to methodologic differences across studies, such as inconsistent follow-up intervals, divergent methods for assessing smoking, reductions in baseline smoking rates in the population over time, and differences between the samples in demographic or medical variables. Recent prospective studies that defined smoking as taking a single puff of a cigarette in the past 30 days have reported rates of continued smoking to be 25% to 48% for head and neck cancer patients [66] [69] [70] [71] and 35% to 40% for lung cancer patients. [68] [70] Last, persistent tobacco use has been documented among 69% of bladder cancer patients,[59] 40% of cervical cancer patients,[58] 20% of adult cancer survivors,[72] and 17% to 20% of survivors of childhood cancers. [73] [74] [75] [76]

Factors Related to Smoking Cessation among Cancer Patients

Identifying factors that influence smoking behavior among cancer patients is essential for developing and implementing smoking cessation interventions for this population. In the next few sections, we review the available literature concerning demographic, medical, and psychological correlates of smoking cessation among cancer patients.

Demographic Variables

Studies that have assessed demographic correlates of smoking behavioral among cancer patients have yielded few consistent findings. For example, while older cancer patients and survivors were more likely to remain abstinent in several studies, [72] [77] this relationship has not been replicated in other studies, [59] [70] [78] or the opposite result has been reported [74] [79] Likewise, while higher educational achievement has been linked with greater abstinence by some, [74] [77] this relationship has not been replicated by others, [59] [70] [71] [78] and one study found the opposite relationship.[65] Furthermore, aside from one study that reported that female cancer survivors were more likely to quit smoking, gender has not been found to be a predictor of smoking cessation among cancer patients. [61] [65] [66] [70] [77] [78]

Smoking history variables (e.g., amount, duration, and level of nicotine dependence) have also been evaluated as correlates of smoking behavior among cancer patients. Amount and duration of tobacco use have been associated with the likelihood of cessation among cancer patients by some studies[74] but not by others. [59] [65] In contrast, several studies have shown that patients with a lower level of nicotine addiction show a greater ability to quit smoking. [66] [70] [78] [79] Last, alcohol use has been examined as a correlate of smoking behavior, particularly among head and neck cancer patients, since many head and neck cancer patients abuse (or at least heavily use) alcohol.[80] Vander Ark and colleagues[71] found that heavy alcohol use was a significant predictor of continued smoking by head and neck cancer patients. Chan and colleagues[62] also reported that concurrent alcohol use predicted future smoking. However, this relationship was not found in other studies of head and neck cancer patients. [61] [77] [79]

Medical Variables

The relationship between disease-related variables and smoking among cancer patients has also been evaluated; however, few consistent findings have emerged. For example, higher rates of abstinence from tobacco use have been noted among head and neck cancer patients with a more advanced disease stage.[65] Similar results were reported in a study with bladder cancer patients.[59] However, several other studies with head and neck cancer patients and lung cancer patients have not replicated this result. Some studies have reported that multimodal medical therapy (e.g., surgery plus radiation) increases quit rates, [65] [71] while other studies indicate that it is the presence of surgery that underlies higher cessation rates (compared to radiation alone[79]). Although this had not been as adequately studied, three studies indicate that as time elapses from the point of diagnosis, the risk of relapsing to smoking increases. [70] [78] [81]

Psychological Variables

Several studies have also examined psychological correlates of smoking among cancer patients. Head and neck and lung cancer patients who exhibit higher motivation to quit (typically assessed by using the stage-based measure derived from the transtheoretical model) show higher rates of smoking cessation. [66] [79] [82] Beliefs about smoking behavior have also been correlated with tobacco use among cancer patients. Christensen and colleagues[61] examined whether perceived control (i.e., believing that future health outcomes are affected by one's behavior) and self-blame (i.e., attributing the cause of the diagnosis to one's behaviors) influenced smoking behavior among head and neck cancer patients. A significant interaction effect was detected: A greater proportion of patients with high levels of self-blame and low levels of perceived control continued to smoke compared to patients with high levels of self-blame but high levels of perceived control (64% versus 25%, respectively).[61] Schnoll and colleagues[78] reported that head and neck cancer patients who report higher quitting self-efficacy (i.e., confidence in their ability to quit) are more likely to abstain from smoking, a finding that was also reported in a prospective study with head and neck cancer patients.[66] Risk perceptions concerning the adverse health effects of tobacco use may be particularly important to address among head and neck cancer patients. In a cross-sectional study, lower perceived risk (e.g., for disease recurrence) was related to a greater likelihood of continued smoking among head and neck cancer patients,[78] a result that was replicated in a prospective study.[70] Lower levels of quitting pros (i.e., advantages of quitting) and higher levels of quitting cons (i.e., disadvantages of quitting) and fatalistic beliefs (i.e., believing that there is no use in quitting) have also been associated with a greater likelihood of continued smoking;[78] higher levels of quitting cons, moreover, predicted persistent smoking and relapse prospectively.[70]

Several studies have shown that negative affect, typically measured by symptoms of depression and anxiety, predict smoking among cancer patients. Cross-sectional studies associated negative mood measured by self-report instruments (e.g., the Hospital Anxiety and Depression Scale) with smoking among head and neck cancer patients. [78] [80] [83] One prospective study reported that patients who lapsed to smoking were significantly more likely to report anxiety in the week prior to a lapse compared to patients who maintained abstinence.[66] A more recent prospective study, which followed a sample of head and neck cancer patients for 15 months, found that patients who continued to smoke had greater negative mood as compared to nonsmokers.[69]

Smoking Cessation Interventions for Cancer Patients

Despite the high rate of persistent tobacco use among cancer patients and the growing recognition of the adverse effects on clinical outcomes for patients who continue to smoke, relatively few randomized clinical trials have evaluated the efficacy of smoking cessation interventions for cancer patients ( Table 27-2 ).


Table 27-2   -- Overview of Smoking Cessation Interventions for Cancer Patients

Study Authors (Year)

Study Population

Study Design and Treatment Groups

Main Results

Gritz et al. (1993)[79]

  

 

N = 186

  

 

Newly diagnosed head and neck cancer patients

Randomized trial in which participants received either one session of “usual care” physician quit advice or an “enhanced” physician quit advice intervention + 6 booster sessions.

  

 

12-month follow-up (biochemically confirmed; n = 114) continuous abstinence rates: usual care = 77%; intervention = 64%.

  

 

No significant difference in quit rates between groups.

Stanislaw and Wewers (1994)[84]

  

 

N = 26

  

 

Patients with various cancers undergoing surgery

Randomized trial in which participants were assigned to usual care or an intervention that consisted of three in-person sessions and five weekly phone calls.

  

 

5-week (biochemically confirmed) quit rates: experimental group was 75% (9/12) versus 43% (6/14) for the control group.

  

 

Difference in quit rates was statistically significant (P < 0.1).

Griebel et al. (1998)[85]

  

 

N = 28

  

 

Patients with various cancers undergoing surgery

Randomized trial in which participants were assigned either to receive usual care or a one-time 20-minute, postoperative smoking cessation session with an oncology nurse + 5 weekly 10-minute booster phone calls.

  

 

6-week (biochemically confirmed) abstinence rate: 21% (3/14) for experimental group and 14% (2/14) for usual care recipients.

  

 

Quit rate differences between groups not statistically significant.

Schnoll et al. 2005[86]

  

 

N = 109

  

 

Head and neck or lung cancer patients

  

 

Randomized trial that compared the efficacy of a cognitive-behavioral therapy (CBT) intervention with a general health education (GHE) intervention for smoking cessation among cancer patients.

  

 

CBT participants received one in-person session and three telephone counseling sessions that were tailored to their barriers to cessation. GHE participants received general quitting advice. All participants received transdermal nicotine.

No significant differences in cessation rates between the CBT and GHE groups were observed at 1-month (45% versus 47%, respectively) or 3-month (43% versus 39%, respectively) follow-up.

Schnoll et al., 2003[87]

  

 

N = 432

  

 

Patients with various cancers

Randomized trial that compared the effectiveness of a physician-based intervention in which the AHRQ 5 A's was delivered versus usual care (brief quit advice).

No significant differences in cessation rates between the physician-based intervention and the usual care condition were observed at the 6-month (14% versus 12%, respectively) and 12-month (13% versus 14%, respectively) follow-up assessments.

Wakefield et al. (2004)[88]

  

 

N = 137

  

 

Patients with various cancers

Randomized trial in which participants were assigned to receive either brief quit advice control condition (brochure + referral to a quit-line; n = 63) or a motivational interviewing experimental condition (n = 74) in which they booklets received specific cessation advice and targeted to cessation for cancer patients via telephone and in-person counseling. NRT was provided to those who smoked >15 cigarettes per day.

  

 

At 3-month follow-up, 7% of the motivational interviewing and 6% of the control group recipients had biochemically confirmed abstinence.

  

 

Differences in group quit rates were not statistically significant.

  

 

Intervention group was significantly more likely than control group to report making a quit attempt (86% versus 62%, respectively).

Emmons et al. (2005)[89]

  

 

N = 796

  

 

Childhood cancer survivors who smoked

Randomized trial in which participants were assigned to either a self-help smoking cessation intervention (physician letter + cessation brochure) or a peer-delivered telephone counseling intervention (up to 6 phone calls tailored to individual's stage of change delivered over 7 months). NRT was also offered to counseling intervention group.

  

 

At 3-months follow-up, counseling group had significantly higher quit rates as compared to self-help group (11% versus 5%).

  

 

At 12-month follow-up, counseling group still had higher quit rates (11% versus 7%, respectively), but differences were not statistically significant.

 

 

The first study, with 186 head and neck cancer patients, randomized patients to either “usual care” physician quit advice (e.g., risks of continued smoking and benefits of cessation) or an “enhanced” physician quit advice intervention that included expression of confidence in the patient's ability to quit, a written quit date contract, tailored self-help booklets, and booster advice to remain abstinent.[79]The results showed extremely high continuous quit rates (biochemically confirmed) for both conditions at a 12-month follow-up (usual care = 77%, intervention = 64%), in part owing to strong physician quit advice provided in both study conditions and the inclusion of patients who had not smoked for up to 1 year prior to study recruitment. In a second study, Stanislaw and Wewers[84] randomized cancer patients with various tumor sites to either a usual care or an intervention that consisted of three in-person behavioral counseling sessions and five follow-up phone contacts. At 5 weeks, the quit rate (biochemically confirmed) for the experimental group was 75% (9/12), compared to 43% (6/14) for the control group, although the small sample led to a nonsignificant comparison. In the third study, Griebel and colleagues[85] randomized cancer patients with various types of malignancies to either usual care or to a one-time smoking cessation consultation with an oncology nurse (plus five telephone booster calls).[85] After 6 weeks, 21% (3/14) of experimental patients exhibited cotinine-validated abstinence, compared to 14% (2/14) of the patients in the usual care condition. Again, the small sample size could have led to a nonsignificant comparison of quit rates.

More recently, Schnoll and colleagues conducted two randomized smoking cessation clinical trials with cancer patients. The first trial examined a cognitive-behavioral therapy (CBT), which addressed theoretically derived cognitive and emotional variables linked to tobacco use in this population (e.g., self-efficacy, risk perception[86]). Head and neck and lung cancer patients (n = 109) were randomized to either the theoretically based CBT intervention or a general health education (GHE) condition, and all patients received nicotine replacement therapy. Although high quit rates were detected in this trial, no significant difference in 30-day point-prevalence abstinence between the CBT and GHE conditions was detected at either 1-month (45% versus 47%, respectively) or 3-month (43% versus 39%, respectively) follow-up evaluation. The second trial examined the efficacy of a physician-based smoking cessation intervention for cancer patients.[87] Cancer patients (n = 432) were randomized to either usual care or a National Institutes of Health physician-based smoking intervention (i.e., the 5As). At 6-month follow-up, there was no significant difference in quit rates between the usual care (12%) and the intervention (14%) group, and there was no significant difference between the usual care (14%) and the intervention (13.3%) group at the 12-month follow-up.

Wakefield and colleagues examined the use of motivational interviewing for promoting smoking cessation among cancer patients.[88] In this study, 137 cancer patients were randomized to either a control group, consisting of quit advice, self-help brochures, and a referral to a quit line, or an intervention arm that included motivational interviewing, smoking cessation self-help booklets, and NRT. After 6 months, the quit rate for the intervention arm was 6%, compared to 5% for the control arm. In a trial of 796 childhood cancer survivors, patients were randomized to either a self-help arm (quit advice letter and self-help booklet) or an intervention arm that consisted of six phone-based counseling sessions from a childhood cancer survivor plus self-help material, and NRT. Quit rates were higher for the peer-counseling condition than for the self-help condition at 8 months (16.8% versus 8.5%) and at 12 months (15% versus 9%).[89]

Barriers to Smoking Cessation Treatment in Clinical Oncology

Quitting smoking following a cancer diagnosis can improve clinical outcomes for patients, and cancer patients exhibit uniquely high levels of quit motivation,[90] suggesting that this can be a teachable moment for smoking cessation. Unfortunately, a cancer diagnosis has been underutilized as a teachable moment for assisting patients to quit smoking.[3] To facilitate greater attention to promoting smoking cessation among cancer patients, barriers to cessation should be identified, including physician and health care system barriers and patient barriers.

Physician and Health Care System Barriers to Smoking Cessation

Because patients visit physicians or members of the health care team repeatedly and view health care professionals as valuable, credible, and reliable sources of health information, they generally adhere to physician advice.[91] Thus, the health care team is a critical resource for addressing patients’ tobacco use. Recent national surveys, however, indicate that primary care physicians and nurses are not capitalizing on their opportunity to intervene with patients. A national survey of physicians indicated that while most physicians (75%) advise their patients to quit smoking, fewer than one third of physicians recommend pharmacotherapy “often or always,” and fewer than one quarter provide referrals for cessation treatment programs “often or always.”[92] Surveys with oncology nurses yield convergent data; about two thirds of nurses document patient smoking status, one third provide cessation advice, and one quarter recommend NRT.[93]

A number of barriers are likely responsible for a failure to fully capitalize on this opportunity. First, pragmatic limitations can make it challenging for health care professionals to intervene with cancer patients who smoke. Physicians and nurses are extremely busy and have little extra time to provide comprehensive nicotine addiction treatment. Second, a lack of third-party reimbursement for treating nicotine dependence and the expense of ascertaining treatment outside of insurance coverage can undermine commitment from health care professionals to intervene with patients who smoke. Third, certain attitudes that health care professionals have about smoking can undermine the provision of adequate treatment, such as believing that patients are not interested in receiving nicotine dependence treatment, that treatment will be ineffective, that they lack the skills and confidence to intervene, and that it is not part of their professional role. [93] [94] These beliefs, in part, stem from an additional barrier to effective treatment of nicotine dependence by physicians and nurses working with cancer patients, namely, the lack of adequate training for health care providers in methods for treating nicotine dependence.[95] Thus, lack of time, financial coverage, and adequate training and specific beliefs undermine the provision of adequate nicotine addiction treatment for cancer patients. Last, health care providers may view nicotine addiction as an acute condition, rather than a chronic illness, and therefore might not provide the sort of ongoing treatment that is required to help patients to quit smoking.

Patient Barriers to Smoking Cessation

Unique aspects of a cancer diagnosis and its treatment undermine effective smoking cessation. First, a cancer diagnosis can produce significant negative affect (i.e., symptoms of anxiety and depression),[96]which, in turn, can undermine the patient's ability to quit smoking. Likewise, ongoing medical treatment, financial pressures, and family strain or conflict can produce stress that undermines quit motivation or triggers relapse following successful cessation. Last, many patients exhibit a fatalistic attitude about quitting smoking (i.e., what is the use of quitting now since the patient has been diagnosed) and low quitting self-efficacy,[96] which diminishes patient commitment to quitting smoking. Second, since cancer patients might be unwilling to admit to smoking, it can be very difficult to ensure that adequate treatment is provided. Third, most cancer patients show very high levels of nicotine dependence and have been smoking for many decades,[96] making treatment more challenging. Last, many cancer patients experience treatment-related side effects that can make it difficult to utilize nicotine addiction treatments, including the nicotine lozenge or gum or bupropion or varenicline (e.g., difficulty with or an inability to swallow), or they might have medical conditions that prevent the use of pharmacotherapy.

Overcoming Barriers

Reducing the prevalence of tobacco use among cancer patients depends on successfully overcoming both physician and patient barriers to cessation. While physicians and health care professionals should not be expected to devote much time to treating nicotine dependence, they should be expected to assess smoking status, deliver cessation advice, and provide a prescription for pharmacotherapy and/or a referral to a local smoking cessation program as needed. Some professional organizations have revised clinical treatment guidelines for smoking cessation from the 5As to Ask, Advise, Refer (seewww.askadviserefer.org/about.asp) in order to overcome practical constraints for health care providers. Additionally, systems changes, such as including smoking status as a vital sign within patient records, can facilitate easy and continual assessment of patient smoking status, along with chart reminders and incentives for identifying and referring patients for appropriate cessation treatment.

While many comprehensive cancer centers offer smoking cessation treatment services or access to treatment through clinical trials, economic barriers to access remain. However, many major insurance companies and many state Medicare and Medicaid programs now cover smoking cessation treatment, and upward of 30 states have free quit lines, in addition to national hot lines operated by the National Institutes of Health and the American Cancer Society. As such, assessing smoking status and providing quit advice, self-help material, and a treatment referral should be affordable for all facilities; therefore, all patients should receive at least this minimal level of smoking cessation intervention.

Training oncologists in clinical practice guidelines for smoking cessation (i.e., the 5As) enhances physician adherence to practice guidelines[87] and reduces patient smoking.[97] Additional research is needed to identify effective and affordable methods for training health care professionals in treating nicotine dependence. This training should prepare health care professionals to intervene with patients and address beliefs that might discourage compliance with treatment guidelines, such as low patient interest in receiving treatment and the adoption of a chronic disease model for nicotine dependence.

Last, as new smoking cessation treatment programs are designed for cancer patients, the efficacy of these programs could depend on the degree to which they are tailored to address the specific needs of cancer patients. Many cancer patients will require intervention components that address affective barriers to cessation (e.g., bupropion). In addition, supportive therapies and coping skills training programs might be needed for many patients to assist them in avoiding relapse when stressful events are encountered. Behavioral counseling might also need to address fatalistic beliefs or a critical lack of confidence in quitting smoking. Patients must also be made to feel safe and comfortable to share their smoking status, so interventions must be nonjudgmental and nonconfrontational (i.e., motivational interviewing). Finally, treatments might need to be relatively intense (e.g., combination pharmacotherapy) to address level of nicotine dependence and be continuously provided for an extended period of time. However, practitioners must consider potential treatment side effects and medical contraindications when selecting a particular treatment approach for patients.

PUBLIC POLICY EFFORTS TO REDUCE CIGARETTE CONSUMPTION

A variety of public policy initiatives, such as bans on tobacco advertising, increased taxation on cigarettes, and clean air laws that ban smoking in public places, have come to the fore as being important legislative tools to reduce cigarette consumption. A brief review of these approaches is provided here.

Tobacco Advertising

Exposure to tobacco advertising has been shown to promote experimentation and the development of a regular smoking habit among adolescents, [98] [99] as well as continued smoking among adults.[100]Consistent with these data is evidence that national bans on tobacco advertising in countries such as Norway, Finland, New Zealand, and France resulted in a 14% to 37% drop in cigarette consumption.[101]Likewise, bans on tobacco advertising in the United States have correlated with a decline in cigarette consumption. However, there are concerns that partial tobacco advertising bans (e.g., banning only outdoor advertising) might serve to exponentially increase tobacco advertising through other venues such as print media, point-of-purchase advertising, and sponsorships, thus compromising the efficacy of this public health approach to reducing cigarette consumption.[102]

Tobacco Taxes

Excise taxes on cigarettes have been shown to reduce cigarette consumption,[103] federal level tax increases being more effective than increases at the state level.[103] Data also suggest that a 10% increasein the price of cigarettes would equate to an 8% decline in smoking prevalence among low-income adults and a 4% decline among higher-income adults.[104] In a random-digit-dial telephone survey of 10,000 New York residents, almost half of respondents who smoked reported that they reduced the number of cigarettes they had smoked in response in an increase in cigarette prices;[105] this response was more pronounced among non-Caucasians, people with low incomes, and those without a high school education.[105] Collectively, these data support the use of increased cigarette taxes as a strategy for reducing cigarette consumption.

Smoking Bans

Given evidence that secondhand smoke increases cancer risk, bans on smoking in public places and workplaces are considered appropriate strategies to minimize the negative health effects from secondhand smoke.[106] Smoking bans in countries such as Ireland, Italy, Sweden, and New Zealand and 13 U.S. states have provided the opportunity to assess the health effects of smoke-free environments, and the results have been encouraging. Specifically, Farrelly and colleagues reported on saliva cotinine (an indicator of nicotine exposure) levels in a sample of New York hospitality workers before and after the smoking ban. Results showed a significant decline in nicotine exposure following the ban.[107] These data are consistent with those of a similar study conducted in Ireland.[108] With regard to any positive health effects from living in an area with a smoke-free policy, one study conducted in the town of Helena, Montana, showed a significant decline in hospital admissions for myocardial infarction for a 6-month period while the smoke-free policy was in place compared to the same 6-month period in the previous years when the smoke-free policy was not in place.[109] Notably, hospital admissions for myocardial infarction in the areas outside Helena where the smoke-free policy was not in place showed a nonsignificant increase.[109]

FUTURE DIRECTIONS AND CONCLUSIONS

The potential increases in tobacco use worldwide, in combination with the suboptimal response to currently approved medications for nicotine dependence treatment, highlight the need to both develop more efficacious smoking cessation treatments and to improve the use of currently approved treatments. Toward this end, the identification of novel medications that mimic and/or attenuate nicotine's rewarding effects or reduce nicotine withdrawal is underway and most clearly demonstrated by the recent FDA approval of varenicline. There is also evidence for the efficacy of selegiline, fluoxetine, naltrexone, and mecamylamine in certain subgroups of smokers, although current data are limited or conflicting. In terms of improving the efficacy of currently approved treatments for nicotine dependence, research concerning smoker characteristics related to responsiveness to NRTs and the potential development of fast-acting NRTs could help clinicians to prescribe NRT (type, dose, and duration) based on the smoker's characteristics, thereby enhancing NRT effectiveness. Similarly, reduced NRT costs in conjunction with innovative marketing approaches to increase the appeal of, and access to, NRTs could significantly increase utilization of NRT products, in turn, broadening the impact of over-the-counter therapies on the population smoking rate. Finally, although the results from pharmacogenetic studies of treatments for nicotine addiction offer limited potential for individualizing patient care at this point, future research in this pioneering area might eventually lead to substantial breakthroughs for individualized treatments for nicotine addiction and additional significant reductions in the worldwide prevalence of smoking. Nevertheless, given the projections for substantial increases in the rate of tobacco use in developing countries and given the lack of resources in these countries to sustain the needed infrastructure for effective treatment for nicotine dependence, efforts must be directed toward the development of low-cost treatments that can be broadly disseminated. Low-cost treatments for nicotine dependence, coupled with innovative marketing of these treatments, should also be seen as a priority in developed countries to further the important advances that have been made thus far in reducing the rate of tobacco use over the past several decades. Partnerships between pharmaceutical companies and government agencies to develop, test, and market new treatments for nicotine dependence, as has been done with treatments for other medical illnesses and diseases, could be critical if additional significant reductions in the worldwide prevalence of smoking are to be realized.

ACKNOWLEDGMENT

Funding for this article was provided by a Transdisciplinary Tobacco Use Research Grant from the National Cancer Institute and National Institute on Drug Abuse (P50 CA/DA 84718) to Dr. Caryn Lerman.

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