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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.”,C. Everett Koop, M.D., former U.S. Surgeon General,“CIGARETTE SMOKING,TRENDS in ADULT SMOKING, by SEXU.S., 19552006,Trends in cigarette current smoking among persons aged 18 or older,Graph provided by the Centers for Disease Control and Prevention. 1955 Current Population Survey; 19652005 NHIS. Estimates since 1992 include some-day smoking.,Percent,70% want to quit,Male,Female,23.9%,18.0%,20.8% of adults are current smokers,Year,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.,U.S. Department of Health and Human Services. (2004). The Health Consequences of Smoking: A Report of the Surgeon General.,FOUR MAJOR CONCLUSIONS:,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.,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.,ANNUAL U.S. DEATHS ATTRIBUTABLE to SMOKING, 19972001,Centers for Disease Control and Prevention. (2005). MMWR 54:625628.,32%,28%,23%,9%,8%,1%,TOTAL: 437,902 deaths annually,Percentage of all smoking-attributable deaths*,* In 2005, it was estimated that nearly 50,000 persons died due to second-hand smoke exposure.,NICOTINE DISTRIBUTION,Henningfield et al. (1993). Drug Alcohol Depend 33:2329.,Arterial,Venous,Nicotine reaches the brain within 11 seconds.,Nicotine enters brain,Stimulation of nicotine receptors,Dopamine release,DOPAMINE REWARD PATHWAY,Prefrontal cortex,Nucleus accumbens,Ventral tegmental area,Irritability/frustration/anger Anxiety Difficulty concentrating Restlessness/impatience Depressed mood/depression Insomnia Impaired performance Increased appetite/weight gain Cravings,NICOTINE PHARMACODYNAMICS: WITHDRAWAL EFFECTS,Hughes. (2007). Nicotine Tob Res 9:315327.,Most symptoms manifest within the first 12 days, peak within the first week, and subside within 24 weeks.,HANDOUT,QUITTING: HEALTH BENEFITS,Lung cilia regain normal function Ability to clear lungs of mucus increases Coughing, fatigue, shortness of breath decrease,Excess risk of CHD decreases to half that of a continuing smoker,Risk of stroke is reduced to that of people who have never smoked,Lung cancer death rate drops to half that of a continuing smoker Risk of cancer of mouth, throat, esophagus, bladder, kidney, pancreas decrease,Risk of CHD is similar to that of people who have never smoked,2 weeks to 3 months,1 to 9 months,1 year,5 years,10 years,after 15 years,Time Since Quit Date,Circulation improves, walking becomes easier Lung function increases up to 30%,Years of life gained,Age at cessation (years),Prospective study of 34,439 male British doctors Mortality was monitored for 50 years (19512001),On average, cigarette smokers die approximately 10 years younger than do nonsmokers.,Among those who continue smoking, at least half will die due to a tobacco-related disease.,SMOKING CESSATION: REDUCED RISK of DEATH,Doll et al. (2004). BMJ 328(7455):15191527.,TOBACCO USE and the DEVELOPMENT of CANCER,TOBACCO: CANCERS CAUSED by TOBACCO,Lung Larynx Oral cavity and pharynx Esophagus Pancreas,Bladder and kidney Cervix Stomach Bone marrow (acute myeloid leukemia),USDHHS. (2004). The Health Consequences of Smoking: A Report of the Surgeon General.,Sufficient evidence exists to infer a CAUSAL relationship between tobacco use and these cancers.,TOBACCO and CANCER: CARCINOGENS in TOBACCO PRODUCTS,Polycyclic aromatic hydrocarbons (PAHs) Benzopyrene Benzanthracene Tobacco-specific nitrosamines (TSNAs) Aromatic amines Formaldehyde Benzene Vinyl chloride Cadmium Radioactive polonium-210,An estimated 4,800 compounds in tobacco smoke, including 11 proven human carcinogens,Nicotine does NOT cause the ill health effects of tobacco use.,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,TOBACCO and CANCER: MECHANISM of CARCINOGENESIS,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,TOBACCO and CANCER: MECHANISM of CARCINOGENESIS (contd),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,TOBACCO and CANCER: MECHANISM of CARCINOGENESIS (contd),PAHs TSNAs Other carcinogens,Nicotine addiction,DNA adducts,Mutations Other changes,Cancer,Excretion,Normal DNA,Apoptosis,Tobacco use,Metabolic detoxification,Metabolic activation,Repair,Persistence/miscoding,Reprinted with permission. Hecht. J Natl Cancer Inst 1999;91:11941210.,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,TOBACCO USE and the TREATMENT of 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 2050% of patients with cancer continue to smoke after diagnosis A large proportion of patients who quit smoking will relapse after completing their treatment,PREVALENCE of SMOKING AMONG PATIENTS with CANCER,Cancer diagnosis provides an important “window of opportunity” for promoting tobacco cessation.,ANNUAL NUMBER of CANCER DEATHS ATTRIBUTABLE to SMOKING, 1997-2001,Centers for Disease Control and Prevention. (2005). MMWR 54:625628.,Graph provided by American Cancer Society, 2008.,SMOKING and CANCER: TREATMENT, SURVIVAL, QUALITY of LIFE,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.,SMOKING,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,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,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,What is nicotines 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?,HANDOUT,EFFECTS of SMOKING on SECOND 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,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.,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,EFFECTS of SMOKING on QUALITY OF LIFE in PATIENTS WITH CANCER,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,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,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,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,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.,TREATING TOBACCO USE and DEPENDENCE: MEDICATIONS for QUITTING,HANDOUT,TOBACCO DEPENDENCE: A 2-PART PROBLEM,Tobacco Dependence,Treatment should address the physiological and the behavioral aspects of dependence.,Physiological,Behavioral,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,PHARMACOTHERAPY,Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS, May 2008.,Medications significantly improve success rates.,* Includes pregnant women, smokeless tobacco users, light smokers, and adolescents.,“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.”,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.,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,Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS, May 2008.,Recommended treatment is behavioral counseling.,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.,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),Nasal spray Nicotrol NS (Rx) Inhaler Nicotrol (Rx),NRT: PRODUCTS,Patients should stop using all forms of tobacco upon initiation of the NRT regimen.,PLASMA NICOTINE CONCENTRATIONS for NICOTINE-CONTAINING PRODUCTS,0 10 20 30 40 50 60,Time (minutes),Cigarette,Moist snuff,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.,NICOTINE GUM Nicorette (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,NICOTINE GUM: DOSING,Dosage based on current smoking patterns:,NICOTINE GUM: DOSING (contd),NICOTINE GUM: CHEWING TECHNIQUE SUMMARY,Park between cheek & gum,Stop chewing at first sign of peppery taste or tingling sensation,Chew slowly,Chew again when peppery taste or tingle fades,NICOTINE LOZENGE Commit (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,NICOTINE LOZENGE: DOSING,Dosage is based on the “time to first cigarette” (TTFC) as an indicator of nicotine addiction,Use Commit Lozenge 2 mg: If you smoke your first cigarette more than 30 minutes after waking up,Use Commit Lozenge 4 mg: If you smoke your first cigarette of the day within 30 minutes of waking up,NICOTINE LOZENGE: DOSING (contd),NICOTINE LOZENGE: DIRECTIONS for USE,Use according to recommended dosing schedule Place in mouth and allow to dissolve slowly (nicotine release may cause warm, tingling sensation) Do not chew or swallow lozenge. Occasionally rotate to different areas of the mouth. Lozenge will dissolve completely in about 2030 minutes.,Do NOT eat or drink for 15 minutes BEFORE or while using the nicotine lozenge.,TRANSDERMAL NICOTINE PATCH NicoDerm CQ (GlaxoSmithKline); generic,Nicotine is well absorbed across the skin Delivery to systemic circulation avoids hepatic first-pass metabolism Plasma nicotine levels are lower and fluctuate less than with smoking,TRANSDERMAL NICOTINE PATCH: PREPARATION COMPARISON,TRANSDERMAL NICOTINE PATCH: DOSING,TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE,Choose an area of skin on the upper body or upper outer part of the arm Make sure skin is clean, dry, hairless, and not irritated Apply patch to different area each day Do not use same area again for at least 1 week,TRANSDERMAL NICOTINE PATCH: ADDITIONAL PATIENT EDUCATION,Water will not harm the nicotine patch if it is applied correctly; patients may bathe, swim, shower, or exercise while wearing the patch,Do not cut patches to adjust dose Nicotine may evaporate from cut edges Patch may be less e