LUNG CANCER

ELSEVIER Lung cancer 11 (1994) 423-444

Abstracts

Prevention

Randomized placebo-controlled trial of isotretinoin in chemoprerention of bronchial squamous metnplnsll Lee JS, Lippman SM, Benner SE, Lee JJ, Ro JY, Lukeman JM et al. l%oracic/Head/Neck Med. Onml. Dept., M.D. Amierson Cancer Center, Box 80,lSlS Holcombe Blvd. Houston, Ix 77030. J Clin Clncol 1994;12:937-45.

Putpare: Retinoids have Proven chemopreventive efficacy in both preclmical and chnical studies. This trial was designed to confirm the lindmp of en earlier uncontrolled trial thet the. synthetic retinoid etreti~te had msjor activity in reversing squamous mdsplnsio found in the bronchial epithelium of chronic smokers. Putients and Metho& We pro+ectively evaluated 152 smokers with bronchoscopy and obtained biopsies from six sites. Subjects with dysplasia and/or a metaplasia index of greater than 15% were randomly assigned to receive either 1 m&g isotretinoin or placebo daily for 6 months. Of 86 subjects randomized (41 isotretinoin, 45 placebo), 69 were reevaluated at the completion of tmatment. Results: In thegroupasawhole, themetDplasi8 index decreamd over time from a mean f SE of 35.8% f 2.7% at baseline to 28.1% f 3.3 96 at the completion of tr&ment(P=.Olby repeated measures analysis of variance [ANOVA]); a reduction in the met&& index (> 8 96) was noted in both isotretinoin and placebo groups (I9 of 35 (54.3461 and 20 of 34 [58.8%], respectively). Complete reversal of squamous metpplasio was noted in nine subjects from each group. However, the magnitudes of the - metaplasia index changes did not differ significantly in the two treatment groups. In both groups, smoking cessation resulted in significant declines in the extent of squamous met#isin, whereas no significant change in rnetaplasia index was found among those who continued to smoke. Conchion: Squamous metaplasia was frequently observed in bronchial biopsy samples from chronic smokers. From this study, we conclude that isotretinoin has no effect on squamous metnplasin, a Potential intermsdiateend Point ofbronchial carcinogenesis. Although determiniig the exact role of isotretinoin in lung cancer prevention requires further study, the finding that there was P significant decrease in squamous metaplasia in the placebo group emphasizes the critical importance of a placebo-controlled study design in chemopreveation trials using intermediate end Points.

pleural mex&&ana and exposure to a&e&w Evnlutttlort from work hi&&s and analysis of asbestos bodies in bronchoalveolar lavage fluid or hmg tissue in 131 patients P&on JC, Grlowski E, Iwatsubo Y, Billon-GalIand MA, Dufour G, Chanuning’s S et al. INSEEM. Unite 139, Hopital Hem’ Monhr, 51 Av. Marechal L.attre a% Tassingy, 94010 Creteil Gdex. Ckcup Environ Med 1994;51:244-9.

Exposure to asbestos wss evaluated in 131 Patients with pleural

mxlignaat meeotbeliome in theParis xrm behveea 1986 end 1992 using data from a detailed specific queetionnaire and light microscopy analysis of the retention of a&estos bodies in bronchoalveolar lavage fluid or lung tissue. Frobable or definite exposure to significant levels of asbestos dust was identified in only 48 (36.6 96) subjects, and significant ssbestos body counts (above 1 asbestos body/ml in bronchoalveolar lavage fluid or 1000 asbestos bodies/g of dry lung tissue) were found in only 45 (34.3 96) subjects. Overall 50 subjects had experienced exposure to only low levels of asbestos or no exposure at all and showed no significantretentionofas+tcebodiesinthebiologicalsampleanalysed. Previous studies have shown that light microscoPy may be uselid in the identification of subjects with previous exposure to asbestos. In this study, apart fmm cases with obvious exposure to asbestos, a large group of subjects seemed to have a history of exposure or lung retention of asbestos bodies suggestive of very low levels of cumulative exposure, similar to those described in the general Population.

The B-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: Smokers and asbestos-exposed work= Ornan GS, Goodmsa G, Thornquist M, Grizzle J, Rosenstock L, Bamhart S et al. CARETCooduating Center, Fred Hutchinson Cancer Research Cm., SeartIe, WA 98104. Cancer Res 1994;54:Suppl2038s- 43s.

CARET is a multicenter, two-armed, double-masked random&d chemoprevention trial in Seattle, Portland, San Francisco, Baltimore., Connecticut, and Irvine, to test whether oral administration of D- carotene (30 mg/day) plus retinyl pshnitate (25,000 IU/day) can decrease the incidence of lung cancer in high risk Populations, namely, heevysmokasandasbestos-exposedwollters.Theint~entioncombines theantioxidantactionof&camteneandthetumorsupptessormechanism of vitamin A. As of April 30, 1993, CARET had randomized 1,845 participants in the 1985-1988 pilot phase plus 13,260 ‘efficacy’ participants since 1989; of these, 4,000 are asbestos- exposed males and 11,105 are smokers end former smokers (44 % female). Accrual is complete everywhere except Irvine, which was the lest center edded (1991), and the safety profile of the regimen to date hss been excellent. With 14,42Osmokers, 4,010asbestos-exposed~articipants, and 114,100 person-ye&s through February 1998, we expect CARET to be capable of detecting a 23% reduction in lung cancer incidence in the two populations combined and 27, 49, 32, and 35% reductions in the smokers, female smokers, male smokers, and asbestos-exposed subgroups, respectively. CARET is highly complementary to the a- tocopheml-B-camtene study in Finlend end the Harvard Physicians HealthShrdy(6-cprotmealone)intheNationalCMcerInstituteport~lio of major cancer chemoprevention trials.