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Recruitment for the beta-carotene and retinol efficacy trial (CARET) to prevent lung cancer in smokers and asbestos-exposed workers.

1992; National Institutes of Health; Volume: 156; Issue: 5 Linguagem: Inglês

Gilbert S. Omenn, Gary E. Goodman, James E. Grizzle, Mark Thornquist, Linda Rosenstock, Scott Barnhart, Gregory M. Anderson, John R. Balmes, James E. Cone, Martin G. Cherniack,

Cancer Risks and Factors

Alerts, Notices, and Case Recruitment for the 3-Carotene and Retinol Efficacy Trial (CARET) to Prevent Lung Cancer in Smokers and Asbestos-Exposed Workers GILBERT S. OMENN, MD, PhD, GARY GOODMAN, MD JAMES GRIZZLE, PhD, MARK THORNQUIST, PhD LINDA ROSENSTOCK, MD, SCOTT BARNHART, MD GARNET ANDERSON, PhD Seattle, Washington JOHN BALMES, MD, JAMES CONE, MD San Francisco, California MARTIN CHERNIACK, MD, MARK CULLEN, MD New Haven, Connecticut ANDREW GLASS, MD, BARBARA VALANIS, PhD Portland, Oregon JAMES KEOGH, MD Baltimore, Maryland FRANK MEYSKENS, Jr, MD, JAMES WILLIAMS, Jr, MD Orange, California THERE ARE THREE major lung cancer chemoprevention trials under way worldwide. One, the f-Carotene and Retinol Effi- cacy Trial (CARET), is recruiting subjects primarily in Cali- fornia, Oregon, and Washington. Our purpose in this article is to share information about the design of CARET and the recruitment strategy and to address some questions physi- cians may raise about their patients who participate in CARET. The investigators welcome referrals to the CARET study centers in Irvine, San Francisco-Vallejo-Santa Clara, Portland, and Seattle (as well as Baltimore and New Haven). Lung cancer is the number one cancer killer of both men and women in the United States and in an increasing number of other countries. Lung cancers account for 27% of all can- cer deaths and 6% of total deaths in the United States, an estimated 143,000 deaths in 1991.1 Despite aggressive ef- forts at early diagnosis and multimodality therapy, the five- year survival rate from lung cancers remains miserably low, about 15%.2 Unlike most common cancers, the causes of lung cancer are well established.35 Thus the National Can- cer Institute has placed highest priority on the prevention of lung cancer. Primary prevention requires preventing the initiation of cigarette smoking, assisting cessation of smok- ing, and protecting people from exposures to asbestos, radon, arsenic, and a few other known pulmonary chemical carcinogens. (Omenn GS, Goodman G, Grizzle J, et al: Recruitment for the (3-Carotene and Retinol Efficacy Trial (CARET) to prevent lung cancer in smokers and in asbestos-exposed workers. West J Med 1992 May; 156:540-544) From the Fred Hutchinson Cancer Research Center, Cancer Prevention Research Unit, and the University of Washington Schools of Public Health and of Medicine, Seattle (Drs Omenn, Goodman, Grizzle, Thomquist, Rosenstock, Bamhart, and An- derson); the Department of Medicine, University of Califomia, San Francisco (Drs Balmes and Cone); the Department of Medicine, Yale University, New Haven, Con- necticut (Dr Chemiack); Kaiser Permanente Center for Health Research, Portland, Oregon (Drs Glass and Valanis); the Department of Medicine, University of Maryland, Baltimore (Dr Keogh); and the Department of Medicine and Cancer Center, University of Califomia, Irvine, Orange (Drs Meyskens and Williams). This project is supported by grant CA 34847 from the National Cancer Institute. Reprint requests to Gilbert S. Omenn, MD, PhD, School of Public Health and Community Medicine, SC-30, University of Washington, Seattle, WA 98195. Reports For tens of millions of Americans who have already in- curred decades of cigarette smoking exposure and several million Americans who have had considerable occupational exposures to asbestos, especially in West Coast seaports, so- called secondary prevention is essential to overcoming the risk factors already at work. About 75% of men and 50% of women between 55 and 64 years of age are current or former smokers.6 Without secondary prevention, the increased risk of lung cancer does not decline in former smokers after smoking ceases, even though the relative risks do decline compared with continuing smokers or with persons who have never smoked.7 Among workers already exposed to asbestos, 4,000 to 6,000 are projected to die of lung cancer per year at least until the year 2000 and up to 8,000 to 10,000 will die of all asbestos-related cancers per year.8'9 The rationale for cancer chemoprevention programs is based on interrupting late stages of promotion and progres- sion in the multistage process of carcinogenesis. Such actions are exactly what is needed for high-risk persons to take ad- vantage of the latent period (or time bomb ) of 20 to 40 years between first exposure and peak risk for lung cancer. Among the multiple classes of chemicals with apparent che- mopreventive activity, vitamin A (retinol) and fl-carotene are leading candidates for efficacy in human beings. 10-12 As de- scribed elsewhere, studies in animals, epidemiologic analy- ses, cell culture experiments, and short-term clinical trials to reverse bronchial metaplasia or buccal mucosa cell micro- nuclei have laid a strong foundation for direct intervention trials. 13 Three potentially definitive clinical chemoprevention tri- als, supported by the US National Cancer Institute, are under way. The Harvard Physicians Study, which was initiated to assess the effect of aspirin on heart disease, was continued to ascertain the effect of f-carotene on overall cancer incidence in 22,000 physicians. The a-Tocopherol-fl-Carotene Study was established to test the combination of f-carotene plus vitamin E in the chemoprevention of lung cancer in 29,000 smokers in Finland. Finally, the CARET trial was designed to test the combination of f-carotene and vitamin A in 18,000 smokers and asbestos-exposed workers. The design and re- cruitment strategy for CARET are described herein. Subjects in chemoprevention trials are healthy volunteers without cancer, not patients who might tolerate considerable discomfort or risk. Because the risk of lung cancer, even among high-risk asbestos-exposed smokers, is on the order of 1 per 100 per year, it is essential that a chemopreventive regimen be shown to have no major objective or subjective side effects. Design of CARET CARET is a two-armed, double-blind, randomized che- moprevention trial to test the hypothesis that the oral admin- istration of f-carotene, 30 mg per day, plus retinol, 25,000 IU per day, will decrease the incidence of lung cancer in heavy smokers and asbestos-exposed workers who have smoked. 14 5 Choice of Agents The presumed mechanisms of action of fl-carotene and of vitamin A (retinol) are attractive and complementary. fl-Car-