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Rx for CHANGE. Clinician-Assisted Tobacco Cessation for Patients with Cancer. is the chief, single, avoidable cause of death in our society and the most important public health issue of our time.”. “CIGARETTE SMOKING…. C. Everett Koop, M.D., former U.S. Surgeon General.

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  1. Rx for CHANGE Clinician-Assisted Tobacco Cessationfor Patients with Cancer

  2. is the chief, single, avoidable cause of death in our society and the most important public health issue of our time.” “CIGARETTE SMOKING… C. Everett Koop, M.D., former U.S. Surgeon General

  3. TRENDS in ADULT SMOKING, by SEX—U.S., 1955–2006 Trends in cigarette current smoking among persons aged 18 or older 20.8% of adults are current smokers Male Percent 23.9% Female 18.0% Year 70% want to quit Graph provided by the Centers for Disease Control and Prevention. 1955 Current Population Survey; 1965–2005 NHIS. Estimates since 1992 include some-day smoking.

  4. 2004 REPORT of the SURGEON GENERAL:HEALTH CONSEQUENCES OF SMOKING Smoking harms nearly every organ of the body, causing many diseases and reducing the health of smokers in general. Quitting smoking has immediate as well as long-term benefits, reducing risks for diseases caused by smoking and improving health in general. Smoking cigarettes with lower machine-measured yields of tar and nicotine provides no clear benefit to health. The list of diseases caused by smoking has been expanded. FOUR MAJOR CONCLUSIONS: U.S. Department of Health and Human Services. (2004). The Health Consequences of Smoking: A Report of the Surgeon General.

  5. HEALTH CONSEQUENCES of SMOKING Cancers Acute myeloid leukemia Bladder and kidney Cervical Esophageal Gastric Laryngeal Lung Oral cavity and pharyngeal Pancreatic Pulmonary diseases Acute (e.g., pneumonia) Chronic (e.g., COPD) Cardiovascular diseases Abdominal aortic aneurysm Coronary heart disease Cerebrovascular disease Peripheral arterial disease Reproductive effects Reduced fertility in women Poor pregnancy outcomes (e.g., low birth weight, preterm delivery) Infant mortality Other effects: cataract, osteoporosis, periodontitis, poor surgical outcomes U.S. Department of Health and Human Services. (2004). The Health Consequences of Smoking: A Report of the Surgeon General.

  6. HEALTH CONSEQUENCES of SMOKELESS TOBACCO USE Periodontal effects • Gingival recession • Bone attachment loss • Dental caries Oral leukoplakia Cancer • Oral cancer • Pharyngeal cancer Oral Leukoplakia Image courtesy of Dr. Sol Silverman - University of California San Francisco Use of alcohol in combination with moist snuff increases the risk of oral cancers.

  7. ANNUAL U.S. DEATHS ATTRIBUTABLE to SMOKING, 1997–2001 Percentage of all smoking-attributable deaths* 32% 28% 23% 9% 8% <1% TOTAL: 437,902 deaths annually * In 2005, it was estimated that nearly 50,000 persons died due to second-hand smoke exposure. Centers for Disease Control and Prevention. (2005). MMWR 54:625–628.

  8. NICOTINE DISTRIBUTION Arterial Venous Nicotine reaches the brain within 11 seconds. Henningfield et al. (1993). Drug Alcohol Depend33:23–29.

  9. DOPAMINE REWARD PATHWAY Prefrontal cortex Dopamine release Stimulation of nicotine receptors Nucleus accumbens Ventral tegmental area Nicotine enters brain

  10. NICOTINE PHARMACODYNAMICS: WITHDRAWAL EFFECTS • Irritability/frustration/anger • Anxiety • Difficulty concentrating • Restlessness/impatience • Depressed mood/depression • Insomnia • Impaired performance • Increased appetite/weight gain • Cravings Most symptoms manifest within the first 1–2 days, peak within the first week, and subside within 2–4 weeks. HANDOUT Hughes. (2007). Nicotine Tob Res 9:315–327.

  11. QUITTING: HEALTH BENEFITS Time Since Quit Date Circulation improves, walking becomes easier Lung function increases up to 30% Lung cilia regain normal function Ability to clear lungs of mucus increases Coughing, fatigue, shortness of breath decrease 2 weeks to 3 months 1 to 9 months Excess risk of CHD decreases to half that of a continuing smoker 1 year Risk of stroke is reduced to that of people who have never smoked 5 years Lung cancer death rate drops to half that of a continuing smoker Risk of cancer of mouth, throat, esophagus, bladder, kidney, pancreas decrease 10 years Risk of CHD is similar to that of people who have never smoked after 15 years

  12. SMOKING CESSATION: REDUCED RISK of DEATH • Prospective study of 34,439 male British doctors • Mortality was monitored for 50 years (1951–2001) On average, cigarette smokers die approximately 10 years younger than do nonsmokers. Years of life gained Among those who continue smoking, at least half will die due to a tobacco-related disease. Age at cessation (years) Doll et al. (2004). BMJ 328(7455):1519–1527.


  14. TOBACCO: CANCERS CAUSED by TOBACCO • Bladder and kidney • Cervix • Stomach • Bone marrow(acute myeloid leukemia) • Lung • Larynx • Oral cavity and pharynx • Esophagus • Pancreas Sufficient evidence exists to infer a CAUSAL relationship between tobacco use and these cancers. USDHHS. (2004). The Health Consequences of Smoking: A Report of the Surgeon General.

  15. TOBACCO and CANCER: CARCINOGENS in TOBACCO PRODUCTS An estimated 4,800 compounds in tobacco smoke, including 11 proven human carcinogens • Polycyclic aromatic hydrocarbons (PAHs) • Benzopyrene • Benzanthracene • Tobacco-specific nitrosamines (TSNAs) • Aromatic amines • Formaldehyde • Benzene • Vinyl chloride • Cadmium • Radioactive polonium-210 Nicotine does NOT cause the ill health effects of tobacco use.

  16. TOBACCO and CANCER: MECHANISM of CARCINOGENESIS • Compounds in tobacco function as • Carcinogens • Initiate tumor growth • Tumor promoters • Stimulate the development of established tumors • Co-carcinogens • Enhance the mutagenic potential of carcinogens; possess little or no direct carcinogenic activity • Irritants • Induce inflammation and compromise tissue integrity

  17. TOBACCO and CANCER: CELL DIVISION A cancer cell dividing its chromosomes (shown in white) into two new cells Image courtesy of Dr. Paul D. Andrews / University of Dundee

  18. TOBACCO and CANCER: MECHANISM of CARCINOGENESIS (cont’d) • Formation of DNA adducts • Covalent binding product of carcinogen (or its metabolite) to DNA • Leads to miscoding and point mutations • Mutations of oncogenes or tumor suppressor genes can lead to uncontrolled cellular growth and development of cancer

  19. TOBACCO and CANCER: MECHANISM of CARCINOGENESIS (cont’d) Nicotine addiction PAHs TSNAs Other carcinogens Tobacco use Metabolic detoxification Excretion Metabolic activation Repair DNA adducts Normal DNA Persistence/miscoding Apoptosis Cancer Mutations Other changes Reprinted with permission. Hecht. J Natl Cancer Inst 1999;91:1194–1210.

  20. TOBACCO USE and the DEVELOPMENT of CANCER: SUMMARY • Tobacco products cause a variety of cancers • Carcinogens present in tobacco products are responsible for these cancers • Carcinogenesis likely involves a multistep process: • Formation of DNA adducts • Permanent cellular mutations • Unregulated cellular growth


  22. PREVALENCE of SMOKING AMONG PATIENTS with CANCER • A large proportion of patients are current or former smokers at the time of cancer diagnosis • Prevalence of ever smoking is highest among patients with tobacco-related cancers • 90% -- lung cancer • 80% -- head and neck cancer • 20–50% of patients with cancer continue to smoke after diagnosis • A large proportion of patients who quit smoking will relapse after completing their treatment Cancer diagnosis provides an important “window of opportunity” for promoting tobacco cessation.

  23. ANNUAL NUMBER of CANCER DEATHS ATTRIBUTABLE to SMOKING, 1997-2001 Centers for Disease Control and Prevention. (2005). MMWR 54:625–628. Graph provided by American Cancer Society, 2008.

  24. SMOKING and CANCER:TREATMENT, SURVIVAL, QUALITY of LIFE SMOKING… • Negatively impacts cancer treatment response • Surgery • Radiation • Chemotherapy • Increases odds for development of second primary tumors • Negatively impacts survival outcomes • Reduces quality of life Clinicians can impact cancer outcomes by assisting patients and their family members with quitting smoking.

  25. EFFECTS of SMOKING on CANCER THERAPY: SURGERY • Smoking is associated with poor surgical outcomes • Respiratory complications during anesthesia • Cardiopulmonary complications • Infections and impaired wound healing • Cerebrovascular complications • Increased post-operative intensive care admissions • Cessation interventions before surgery can reduce risk of complications • Best when offered at least 6 weeks prior to surgery

  26. EFFECTS of SMOKING on CANCER THERAPY: RADIATION • Smoking reduces treatment efficacy • Patients who smoke experience increased incidence of complications • Toxicity • Side effects • Overall morbidity • Smoking is associated with reduced survival rates

  27. EFFECTS of SMOKING on CANCER THERAPY: CHEMOTHERAPY • Smoking may decrease the therapeutic effects of chemotherapy and other medications • Drug interactions with smoking -- increased hepatic metabolism (e.g., irinotecan, erlotinib) • More research is needed to delineate effects of smoking on chemotherapy outcomes HANDOUT • What is nicotine’s effects on cancer cells, and how does it impact treatment? • Does the lack of smoking data in patient charts impact our ability to understand the relationship between smoking and outcomes? • How does smokers’ increased risk of co-morbid disease impact their likelihood for entry into clinical trials?

  28. EFFECTS of SMOKING onSECOND PRIMARY TUMORS • Continued smoking after diagnosis increases risk for second primary tumors -- this applies to: • The initial tumor site and other sites • Malignancies related to smoking • Malignancies not related to smoking • Dose-response relationship of intense cigarette use increases the risk for second primary tumors • Continued exposure to tobacco after cancer diagnosis may be the more important risk factor

  29. EFFECTS of SMOKING on CANCER SURVIVAL OUTCOMES • Survival is reduced in patients who smoke • As a direct result of malignancy • As a consequence of other smoking-related disease(s) • Smoking history • >30 pack-years has been shown to be an independent prognostic factor for both short- and long-term survival rates • Tobacco mutagenicity may play a role in the growth and extension of certain cancers • Presents further obstacles for survival Quitting smoking before diagnosis and treatment can positively influence survival.

  30. EFFECTS of SMOKING on QUALITY OF LIFE in PATIENTS WITH CANCER • Smoking after diagnosis negatively impacts • Overall quality of life (QOL) • Risk for co-morbid diseases, which independently have a negative impact on QOL • Symptom distress • Higher in persistent smokers, compared to never smokers

  31. HOW DOES SMOKING CESSATION IMPROVE CANCER PROGNOSIS? • Quitting prior to diagnosis and treatment has a positive influence on prognosis and survival • Examples • Head and neck cancer • Quitting 12 weeks and 1 yr prior to diagnosis reduces mortality by 40% and 70%, respectively • Non-small cell lung cancer • Quitting at any point prior to lung operation is beneficial to prognosis and long-term survival

  32. WHAT FACTORS POSITIVELY INFLUENCE QUITTING in PATIENTS WITH CANCER? • Patient awareness of the link between smoking and their diagnosed smoking-related cancer • Patient concern about recurrent disease and the effects of smoking on treatment success • Advice given in the context of medical care

  33. MORE INTENSIVE or TAILORED INTERVENTIONS MAY BE NEEDED • Patients with cancer tend to have: • Higher levels of nicotine dependence • Higher levels of psychiatric co-morbidity • Higher need for treatment support • High percentage of household smokers • Poorer general health and physical functioning • More stress and emotional distress • Cancer disease-related issues need to be taken into account in treatment decisions and patient monitoring • Impact of smoking on surgery, radiation, and chemotherapy • Systematic advice (from multiple providers), with stepped-care approach for patients experiencing difficulty with quitting

  34. RELAPSE in PATIENTS WITH CANCER • Up to one third or one half of patients will either continue to smoke after diagnosis or relapse after an initial quit attempt • Relapse is often delayed in patients with cancer, compared to healthy patients • Follow-up and monitoring is needed • In relapsers: • Encourage a subsequent quit attempt, to avoid additional post-diagnosis risk due to smoking

  35. SUMMARY: REASONS TO QUIT for PATIENTS WITH CANCER • Reduced risk for complications related to cancer therapy and surgery • Improved survival • Improved quality of life • Reduced risk of second primary tumor(s) TOBACCO CESSATION is an essential component of treatment for patients with cancer.


  37. The addiction to nicotine The habit of using tobacco Treatment Treatment Medications for cessation Behavior change program TOBACCO DEPENDENCE:A 2-PART PROBLEM Tobacco Dependence Physiological Behavioral Treatment should address the physiological and the behavioral aspects of dependence.

  38. PHARMACOLOGIC METHODS: FIRST-LINE THERAPIES Three general classes of FDA-approved drugs for smoking cessation: Nicotine replacement therapy (NRT) Nicotine gum, patch, lozenge, nasal spray, inhaler Psychotropics Sustained-release bupropion Partial nicotinic receptor agonist Varenicline

  39. PHARMACOTHERAPY “Clinicians should encourage all patients attempting to quit to use effective medications for tobacco dependence treatment, except where contraindicated or for specific populations* for which there is insufficient evidence of effectiveness.” * Includes pregnant women, smokeless tobacco users, light smokers, and adolescents. Medications significantly improve success rates. Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS, May 2008.

  40. PHARMACOTHERAPY: USE in PREGNANCY The Clinical Practice Guideline makes no recommendation regarding use of medications in pregnant smokers Insufficient evidence of effectiveness Category C: varenicline, bupropion SR Category D: prescription formulations of NRT “Because of the serious risks of smoking to the pregnant smoker and the fetus, whenever possible pregnant smokers should be offered person-to-person psychosocial interventions that exceed minimal advice to quit.” (p. 165) Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS, May 2008.

  41. PHARMACOTHERAPY: OTHER SPECIAL POPULATIONS Pharmacotherapy is not recommended for: Smokeless tobacco users No FDA indication for smokeless tobacco cessation Individuals smoking fewer than 10 cigarettes per day Adolescents Nonprescription sales (patch, gum, lozenge) are restricted to adults ≥18 years of age NRT use in minors requires a prescription Recommended treatment is behavioral counseling. Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS, May 2008.

  42. NRT: RATIONALE for USE Reduces physical withdrawal from nicotine Eliminates the immediate, reinforcing effects of nicotine that is rapidly absorbed via tobacco smoke Allows patient to focus on behavioral and psychological aspects of tobacco cessation NRT products approximately doubles quit rates.

  43. Polacrilex gum Nicorette (OTC) Generic nicotine gum (OTC) Lozenge Commit (OTC) Generic nicotine lozenge (OTC) Transdermal patch NicoDerm CQ(OTC) Generic nicotine patches (OTC, Rx) NRT: PRODUCTS Nasal spray • Nicotrol NS (Rx) Inhaler • Nicotrol (Rx) Patients should stop using all forms of tobacco upon initiation of the NRT regimen.

  44. PLASMA NICOTINE CONCENTRATIONS for NICOTINE-CONTAINING PRODUCTS Cigarette Moist snuff 0 10 20 30 40 50 60 Time (minutes)

  45. NRT: PRECAUTIONS Patients with underlying cardiovascular disease Recent myocardial infarction (within past 2 weeks) Serious arrhythmias Serious or worsening angina NRT products may be appropriate for these patients if they are under medical supervision.

  46. NICOTINE GUMNicorette (GlaxoSmithKline); generics Resin complex Nicotine Polacrilin Sugar-free chewing gum base Contains buffering agents to enhance buccal absorption of nicotine Available: 2 mg, 4 mg; original, cinnamon, fruit, mint (various), and orange flavors

  47. NICOTINE GUM: DOSING Dosage based on current smoking patterns:

  48. NICOTINE GUM: DOSING (cont’d)

  49. NICOTINE GUM:CHEWING TECHNIQUE SUMMARY Chew slowly Stop chewing at first sign of peppery taste or tingling sensation Chew again when peppery taste or tingle fades Park between cheek & gum

  50. NICOTINE LOZENGECommit (GlaxoSmithKline); generics Nicotine polacrilex formulation Delivers ~25% more nicotine than equivalent gum dose Sugar-free mint (various), cappuccino or cherry flavor Contains buffering agents to enhance buccal absorption of nicotine Available: 2 mg, 4 mg

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