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Impact of smoking intervention on lung function — 4-year-study
s22
Abstracts
cessation courses at the Postgraduate Medical School since 1992 at present. The course concerns the epidemiology of smoking, impact of the active and passive smoking on humans’ health, tobacco smoke composition, and smoking cessation methods, particularly the nicotine replacement therapy. The course fellows are mostly running the smoking cessation clinics which are 50 at present. Smoking cessation results (1995-1996) in one of them will be presented. Smokers (men 130, women 671, most with 15-20 cigarettes smoked daily (74%), were treated with nicotine patches or gums for 3 months in the mean. Their mean nicotine dependence (FTND-Fagerstrbm Test of Nicotine Dependence) score was 8.0 (S.D. 1.68). At one year their proven (CO-carbon monoxide) abstinence rate was 55%. Impact of smoking intervention on lung function - 4-yearstudy Wimberger F, Forstner B, Dorninger HP, Bolitschek J, Aigner K. Pneumological Dept. /General Hospital Elisabethinen Linz, (H.D. Prim. Dr. K Aigner) A-4010 Liru, FadingerstmJe 1. Background: Chronic obstructive pulmonary disease (COPD)
is caused by smoking and its prevalence and mortality reflect the smoking history of the population, though only 15-20% of regular cigarette smokers develop clinically evident COPD. Methods: In a 4-year controlled study we examined the effects of smoking cessation by nicotine replacement therapy on lung function. Cigarette smokers defmed as people who had smoked at least 15 cigarettes per day within the last 3 years, aged 35-60 years, who regarded themselves as healthy and had mild airway obstruction (FEVl/FVC-ratio < 70%; FEVl 55590% predicted) were invited to enter the study (40 smokers average age 43 f 8 years/33 male, seven female). Nicotine-abstinence was biochemically confirmed by urine cotinine and exhaled carbon monoxide levels. Results and Discussion Smoking cessation rates were amongst the highest achieved in international studies. The cross sectional quit rate was 35% (13 male, one female). Decline in forced expiratory volume in 1 s (FEVl) was greater in the persistent smoker group than in the quitter group, ascribable to smoking cessation. However the mean rate of decline in FEVl among continuous smokers of about 60 ml-year 1 was similar to the average of smokers in previous studies. The FEVl of nonsmokers declines at an average of 30 ml-year throughout life. By extrapolation, nonsmokers would be expected to reach symptomatic levels of FEVl by the age of about 120 years. References: Fletcher C, Peto R. The natural history of chronic airflow obstruction. Br Med J 1977;1:1645-1648. Anthonisen NR. Lung Health Study. Am Rev Respir Dis 1989;140:871-872. Expression of MN-tumor associated antigen in resected nonsmall cell lung cancer (NSCLC): a new biomarker of in situ and invasive disease Vermylen P, Roufosse C, Bosschaerts T, Ninane V, Sculier JP, Burny A. Institute Jules Bordet and Universi@ Hospital SaintPierre, Brussels,
Belgium.
We studied the immunoreactive MN expression in 46 resected NSCLC, in normal lung parenchyma in close vicinity to
the tumors and in preneoplastic lesions obtained by fluorescence bronchoscopy in patients at high risk for lung cancer. Primary monoclonal mouse anti-MN antibody (M 75, generously given by Dr. Pastorek) was used for immunohistochemistry in all samples. Cytoplasmic MN overexpression was observed in 83% of the tumours (squamous cell: 20/22, adenocarcinoma: 14/18, bronchioloalveolar carcinoma 2/4 and undifferentiated NSCLC 2/2). No expression was detected in alveolar epithelium whereas bronchial epithelium in close vicinity to the tumors expressed MN antigen in lo/16 cases. Expression of the MN antigen in preneoplastic lesions biopsied in vivo during fluorescence bronchoscopy was restricted to the carcinoma in situ stage. Western blot confirmed the expression of MN in tumours (n = 8) and its absence in matched normal lung. In addition, MN overexpression could be detected in sputum samples, obtained in cancer patients. Altogether, these data confirm that MN tumor associated antigen might represent a useful biomarker for NSCLC. (Supported by FNRS-Tel&vie 9.4587.95,7.4523.96 and V&ale Fondation).
Avicidin’ therapy: high dose systemic radiation with tumor regressions in phase I/II clinical trials of antibody pretargeting. Abrams PG. NeoRx Coqwmtion and Untiersig of Washington Medical
Center,
Seattle,
WA, USA.
Antibody targeted therapy has not been successful in solid tumors. PretargetTM technology uses antibody to target tumor with a receptor (antibody/streptavidin conjugate), and then delivers therapy with a small molecule (biotin/yttrium-90) that binds receptor. In clinical trials this allowed high radiation doses, immediate tumor uptake of radiation, rapid disappearance of unbound radiation and tumor regressions of bulky, chemotherapy-resistant solid tumors to just a single dose. Avicidin” is a Pretarget product consisting of an antibody (NR-LU-lo), raised to small cell lung cancer. The antibody/streptavidin conjugate is injected, and 72 h later the biotin-yttrium is administered. The biotin-yttrium binds the prelocalized streptavidin. In phase I clinical trials, Avicidina was shown to be safe at doses more than five times the MTD of antibodies linked to yttrium by conventional techniques. The typical chemotherapy toxicities of nausea, vomiting, hair loss, and appetite loss were not significant. The usual biologicals’ toxicities of fevers, rigors, and lassitude were absent. Patients with advanced, bulky solid tumors that had failed standard therapies received a single dose of Avicidina. The mass doses of the components were kept constant, but the radiation dose was escalated (15 to 140 mCi/m*) in groups of three patients until dose-limiting toxicity was encountered. Objective tumor regressions were observed in patients with a variety of tumors including hormone refractory prostate cancer, platinum-resistant ovarian cancer, and metastatic colon cancer. A phase II trial in SCLC (as well as prostate and colon cancers) is underway. Supported by NeoRx Corporation, Seattle, WA. AVICIDIN” is a registered trademark and PRETARGETTM is a pending trademark of NeoRx Corporation.
Abstracts
cessation courses at the Postgraduate Medical School since 1992 at present. The course concerns the epidemiology of smoking, impact of the active and passive smoking on humans’ health, tobacco smoke composition, and smoking cessation methods, particularly the nicotine replacement therapy. The course fellows are mostly running the smoking cessation clinics which are 50 at present. Smoking cessation results (1995-1996) in one of them will be presented. Smokers (men 130, women 671, most with 15-20 cigarettes smoked daily (74%), were treated with nicotine patches or gums for 3 months in the mean. Their mean nicotine dependence (FTND-Fagerstrbm Test of Nicotine Dependence) score was 8.0 (S.D. 1.68). At one year their proven (CO-carbon monoxide) abstinence rate was 55%. Impact of smoking intervention on lung function - 4-yearstudy Wimberger F, Forstner B, Dorninger HP, Bolitschek J, Aigner K. Pneumological Dept. /General Hospital Elisabethinen Linz, (H.D. Prim. Dr. K Aigner) A-4010 Liru, FadingerstmJe 1. Background: Chronic obstructive pulmonary disease (COPD)
is caused by smoking and its prevalence and mortality reflect the smoking history of the population, though only 15-20% of regular cigarette smokers develop clinically evident COPD. Methods: In a 4-year controlled study we examined the effects of smoking cessation by nicotine replacement therapy on lung function. Cigarette smokers defmed as people who had smoked at least 15 cigarettes per day within the last 3 years, aged 35-60 years, who regarded themselves as healthy and had mild airway obstruction (FEVl/FVC-ratio < 70%; FEVl 55590% predicted) were invited to enter the study (40 smokers average age 43 f 8 years/33 male, seven female). Nicotine-abstinence was biochemically confirmed by urine cotinine and exhaled carbon monoxide levels. Results and Discussion Smoking cessation rates were amongst the highest achieved in international studies. The cross sectional quit rate was 35% (13 male, one female). Decline in forced expiratory volume in 1 s (FEVl) was greater in the persistent smoker group than in the quitter group, ascribable to smoking cessation. However the mean rate of decline in FEVl among continuous smokers of about 60 ml-year 1 was similar to the average of smokers in previous studies. The FEVl of nonsmokers declines at an average of 30 ml-year throughout life. By extrapolation, nonsmokers would be expected to reach symptomatic levels of FEVl by the age of about 120 years. References: Fletcher C, Peto R. The natural history of chronic airflow obstruction. Br Med J 1977;1:1645-1648. Anthonisen NR. Lung Health Study. Am Rev Respir Dis 1989;140:871-872. Expression of MN-tumor associated antigen in resected nonsmall cell lung cancer (NSCLC): a new biomarker of in situ and invasive disease Vermylen P, Roufosse C, Bosschaerts T, Ninane V, Sculier JP, Burny A. Institute Jules Bordet and Universi@ Hospital SaintPierre, Brussels,
Belgium.
We studied the immunoreactive MN expression in 46 resected NSCLC, in normal lung parenchyma in close vicinity to
the tumors and in preneoplastic lesions obtained by fluorescence bronchoscopy in patients at high risk for lung cancer. Primary monoclonal mouse anti-MN antibody (M 75, generously given by Dr. Pastorek) was used for immunohistochemistry in all samples. Cytoplasmic MN overexpression was observed in 83% of the tumours (squamous cell: 20/22, adenocarcinoma: 14/18, bronchioloalveolar carcinoma 2/4 and undifferentiated NSCLC 2/2). No expression was detected in alveolar epithelium whereas bronchial epithelium in close vicinity to the tumors expressed MN antigen in lo/16 cases. Expression of the MN antigen in preneoplastic lesions biopsied in vivo during fluorescence bronchoscopy was restricted to the carcinoma in situ stage. Western blot confirmed the expression of MN in tumours (n = 8) and its absence in matched normal lung. In addition, MN overexpression could be detected in sputum samples, obtained in cancer patients. Altogether, these data confirm that MN tumor associated antigen might represent a useful biomarker for NSCLC. (Supported by FNRS-Tel&vie 9.4587.95,7.4523.96 and V&ale Fondation).
Avicidin’ therapy: high dose systemic radiation with tumor regressions in phase I/II clinical trials of antibody pretargeting. Abrams PG. NeoRx Coqwmtion and Untiersig of Washington Medical
Center,
Seattle,
WA, USA.
Antibody targeted therapy has not been successful in solid tumors. PretargetTM technology uses antibody to target tumor with a receptor (antibody/streptavidin conjugate), and then delivers therapy with a small molecule (biotin/yttrium-90) that binds receptor. In clinical trials this allowed high radiation doses, immediate tumor uptake of radiation, rapid disappearance of unbound radiation and tumor regressions of bulky, chemotherapy-resistant solid tumors to just a single dose. Avicidin” is a Pretarget product consisting of an antibody (NR-LU-lo), raised to small cell lung cancer. The antibody/streptavidin conjugate is injected, and 72 h later the biotin-yttrium is administered. The biotin-yttrium binds the prelocalized streptavidin. In phase I clinical trials, Avicidina was shown to be safe at doses more than five times the MTD of antibodies linked to yttrium by conventional techniques. The typical chemotherapy toxicities of nausea, vomiting, hair loss, and appetite loss were not significant. The usual biologicals’ toxicities of fevers, rigors, and lassitude were absent. Patients with advanced, bulky solid tumors that had failed standard therapies received a single dose of Avicidina. The mass doses of the components were kept constant, but the radiation dose was escalated (15 to 140 mCi/m*) in groups of three patients until dose-limiting toxicity was encountered. Objective tumor regressions were observed in patients with a variety of tumors including hormone refractory prostate cancer, platinum-resistant ovarian cancer, and metastatic colon cancer. A phase II trial in SCLC (as well as prostate and colon cancers) is underway. Supported by NeoRx Corporation, Seattle, WA. AVICIDIN” is a registered trademark and PRETARGETTM is a pending trademark of NeoRx Corporation.