Presentation on theme: "Smoking Cessation Lung Cancer Symposium 2008 Michael D. Skokan MD Pulmonary and Critical Care Medicine Interventional Bronchoscopy The Oregon Clinic Thoracic."— Presentation transcript:
Smoking Cessation Lung Cancer Symposium 2008 Michael D. Skokan MD Pulmonary and Critical Care Medicine Interventional Bronchoscopy The Oregon Clinic Thoracic Oncology Program, Providence Portland Medical Center
Linking Tobacco and Lung Disease
Lung Cancer History First case of bronchogenic carcinoma by Agricola in 1521 1851 – First case of bronchogenic carcinoma in the U.S. was reported Very rare prior to 1900 211 cases had been reported in the surgical literature by the year 1900 and only 374 cases by 1912 Autopsy series in Dresden Germany –0.3% in 1852 –5.6% in 1952
Tobacco Originated in the Peruvian/Ecuadorian Andes First cultivated BC Spread throughout the Americas prior to the arrival of Columbus Used medicinally, ceremonially, and as an insecticide.
Tobacco Brought back to England in the mid to late 1500s Progressively became more popular A major driving force behind the growth of the American colonies Economic engine behind the American Revolution
1880 – James Bonsack invents mechanical roller for production –120,000 cigarettes per day Buck Duke licensed machine and starts spending 20% of profits on racy advertising –Built a tremendous fortune and worldwide influence
Cigarette consumption Colditz GA et al. (2006) Epidemiology
Political power of tobacco $13.11 Billion spent on advertising 2005 Altria (Philip Morris) has spent more money lobbying Congress than any other business Over $20 million per year lobbying congress, $45,977 per member of Congress Congressmen earn $156,200-$212,100/yr FTC Cigarette Report,
Tobacco: The Human Cost Leading cause of preventable death in US. Smoking mortality is a composite of 4 leading causes of death: heart disease, cancer, cerebrovascular disease, COPD. Smokers who do not quit by age 35 have a 50% of dying of tobacco-related disease. For each of the 22 billion packs sold in US in 1999, $3 was spent on medical care attributable to smoking; $3.73 in productivity
Tobacco Cessation: Benefits Participation in smoking cessation program = decreased all-cause mortality. Rapid decrease in risk of new myocardial events, including sudden death. Proven to decrease the rate of decline of FEV1 in those with COPD. Clear reduction in smoking-related cancer risk.
Benefit of Smoking Reduction Godtfredsen NS. JAMA 2005
Smoking Cessation: Lung Health Study JAMA 1994; 272:1497. COPD detected in smokers with few symptoms by spirometry. Continued smokers had faster decline in lung function Participation in smoking cessation program decreased rate of decline in FEV1 over 4 yrs (34 vs. 63 mL/yr). Rate of decline similar to healthy nonsmokers (28 to 35 mL/yr).
Methods: Advice to Quit and the Dose Response More time spent and more sessions = improved quit rate. PHS Smoking Cessation Guideline 2000 Anything is better than nothing: telephone survey of smokers found only 51% were spoken to about smoking; 15% were offered help in quitting. Goldstein MG. Arch Intern Med 1997.
Office Approach: Self Determination and the “Three Questions” Williams GC. Annals Intern Med ) “What do you understand about the health consequences of smoking?” 2) “Are you ready to quit?” 3) “What would it take for you to stop smoking?”
Cessation: Pharmacotherapy Nicotine replacement therapy (NRT); gum, patch, lozenge, inhaler, nasal spray. Non-NRT: bupropion, nortriptyline, clonidine, naltrexone. All pharmacotherapy approximately doubles cessation rates; choice depends on patient characteristics and preference.
NRT: Nicotine Gum PHS review of 13 studies: OR 1.5 vs. placebo (improved quit-rate 40-60%). Users use a piece Q1-2hrs for 1 st 6 weeks; then one piece Q2-4hrs for 3 weeks; then one piece Q4-8hrs for 3 week. High-dependent smokers do better with 4mg dose (in addition to behavioral support). Herrera N. Chest 1995.
NRT: Lozenge Shiffman S. Annals Intern Med Randomized, controlled trial of 1818 pts. 2 or 4mg based on time to first cigarette (TTFC). Significantly higher rate of abstinence at one year compared to placebo (15 vs. 6%).
NRT: Transdermal Patch 27 studies reviewed by PHS. Effective vs. placebo (OR 1.9). Highest dose patch (21-22mg) sustains blood level of 50% compared to 1.5 PPD. Higher dose may be better: 724 smokers assigned to 21, 14 or 7 mg. Quit rates for 21mg vs. placebo at 4-5 yrs were 12.4 vs. 4.5%. Rates for 14 and 7 mg vs. placebo, not significantly different. Daughton DM. Prev Med 1999.
NRT: High Dose Therapy Dale LC et al. JAMA 1995 RCT of 71 smokers stratified to smoking rate. Blood cotinine levels at baseline and steady state to assess adequacy of nicotine replacement. If > 2 pks/day or cotinine > 300ng/mL; then use 44mg (2 patches). High dose is safe (if insomnia use 16 hrs). Quit rate 45% at one year.
NRT: Nicotine Inhaler 4 studies adequate for PHS and effective vs. placebo (OR 2.5). Each inhaler cartridge contains 10mg and delivers 4mg over 80 inhalations. Not true “inhaler”; most absorbed in mouth. In trials successful pts used 6-16 cartridges a day; best effect with puffing for 20 minutes. Too demanding for high dose smokers.
NRT: Comparison Hajek P. Arch Intern Med 1999 Comparison of nicotine gum, transdermal patch, nasal spray and inhaler in 504 smokers with > 10 cigarettes/day. No difference in withdrawal discomfort, urge to smoke or rates of abstinence. Compliance high for patch; low for gum; very low for spray or inhaler.
Pharmacologic Therapy: Bupropion RCT of 615 pts; Bupropion 150 BID vs. placebo: quit rates > at 7 wks (44 vs. 19%) & at one year (23 vs. 12%). Hurt RD.NEJM Bupropion + NRT better than monotherapy or placebo. Jorenby DE. NEJM 1999.
Bupropion: Real World Swan GE. Arch Intern Med month quit rates 12 month quit rates Bupropion 150mg Bupropion 150mg Bupropion 300mg Minimal counsel Minimal counsel one call one call 23.6% 23.6% 25.7% 25.7% More counsel More counsel five calls five calls 31.4% 31.4% 33.2% 33.2%
Varenicline tartrate Partial agonist of acetylcholine receptor. Stimulates receptor or decrease craving and withdrawal. FDA approval May Launched as Chantix July 2006.
Varenicline vs Bupropion and Placebo Gonzales et al. JAMA 2006
Pooled Phase III Data Varenicline vs. Placebo Value 12 weeks Abstinence 52 weeks Abstinence Relative Risk Absolute Risk Number Needed to Treat (NNT) 48 P value p<0.0001p<0.0001
Pooled Phase III Data Varenicline vs. Bupropion Value 12 week Abstinence 52 week Abstinence Relative Risk Absolute Risk NNT714 P value p<0.0001p<0.0001
Varenicline: Treatment Target quit date one week after initiation of drug. One week dose adjustment (0.5mg days 1-3, 0.5mg BID days 4-7, 1mg BID on day 8). No dose adjustments for liver disease— +renal clearance (0.5mg QD for creat. cl. < 30). No lab monitoring; no drug-drug interactions.
Varenicline: Side Effects Nausea most common: decrease the dose. Possible neuro- psychiatric adverse effects: new warning added. Probably should not use in schizophrenia, bipolar or major depression.
Varenicline: Summary First line treatment for tobacco use. Candidates need to show evidence of motivation. Real-world results not as good; cannot provide the same level of behavioral support.
Overall Approach: 5 A’s Ask: Systematically ID all tobacco users. Advise: urge all smokers to quit. Ask: ask all smokers if he or she is ready to make a quit attempt. Assist: make a plan; utilize any counselling service available; add appropiate drugs. Arrange: set up follow-up. Office visit or call.
Overall Approach Be compassionate and passionate: this is an addiction, not a character issue; it can be done. If not ready to quit, express your concern, make sure they know the issues, move on. If ready to make an attempt, then be aggressive. Set quit date. Work the insurance benefits for behavioral and pharmacologic treatment.
Pharmacotherapy: Clonidine 5 trials reviewed by PHS Clonidine doubled quit rate vs. placebo (OR 2.1). Dosed either oral or transdermal with doses 0.15 to 0.75 mg/day. May be more effective in women (OR 3.0). Not FDA approved; a second-line drug.