Biomedical subjects

G E Goodman

Publications and source records attributed to G E Goodman.

At least 19 recordsLinked to original sources

PubMed2005

Changes in cholesterol and triglyceride concentrations in the Vanguard population of the Carotene and Retinol Efficacy Trial (CARET).

BACKGROUND: The Beta-Carotene and Retinol Efficacy Trial (CARET) was terminated 21 months ahead of schedule due to an excess of lung cancers. Deaths from cardiovascular disease also increased (relative risk=1.26 (95% confidence interval (CI) 0.99-1.61)) in the group assigned to a combination of 30 mg beta-carotene and 25 000 IU retinyl palmitate (vitamin A) daily. The basis for increased cardiovascular mortality is unexplained. DESIGN: We analyzed data on serum lipids, available for 1474 CARET Vanguard participants who were enrolled in the two CARET pilot studies and transitioned to the Vanguard study. Total cholesterol and triglycerides were measured 2 months prior to, 4 and 12 months following randomization, and annually thereafter for up to 7 y. INTERVENTION: In the asbestos-exposed pilot (N = 816), participants were assigned to beta-carotene and retinol or to placebo; in the smokers pilot (N = 1029), participants were assigned to beta-carotene, retinol, a combination, or placebo. RESULTS: Serum cholesterol showed a decline over time in both arms; serum triglycerides had a continuous decline over time in the placebo arm, but an initial increase that persisted in the active arm. Both serum cholesterol concentrations (P < 0.0003) and serum triglycerides (P < 0.0001) were significantly higher in the participants receiving vitamin A and/or a combination of vitamin A and beta-carotene (n = 863) as compared to the placebo group (n = 611). Those in this active intervention group had an average cholesterol concentration 5.3 mg/dl (0.137 mmol/l) higher than those in the placebo arm. CONCLUSION: The differences in cholesterol and triglyceride concentrations between the groups following randomization may account in part for the unexpected excess in cardiovascular deaths seen in the active intervention arm of CARET.

Antioxidants↗

PubMed2002

Lung cancer. 1: prevention of lung cancer.

Cancer of the lung causes more deaths from cancer worldwide than at any other site. The environmental, genetic, and dietary risk factors are discussed and progress in chemoprevention is reviewed. A better understanding of the molecular events that occur during carcinogenesis has opened up new areas of research in cancer prevention and a number of biochemical markers of high risk individuals have been identified. It is predicted that greater success in chemoprevention will be achieved in the next decade than in the last.

Biomarkers, Tumor↗

PubMed2001

Randomized phase III intergroup trial of isotretinoin to prevent second primary tumors in stage I non-small-cell lung cancer.

BACKGROUND: Promising data have suggested that retinoid chemoprevention may help to control second primary tumors (SPTs), recurrence, and mortality of stage I non-small-cell lung cancer (NSCLC) patients. METHODS: We carried out a National Cancer Institute (NCI) Intergroup phase III trial (NCI #I91-0001) with 1166 patients with pathologic stage I NSCLC (6 weeks to 3 years from definitive resection and no prior radiotherapy or chemotherapy). Patients were randomly assigned to receive a placebo or the retinoid isotretinoin (30 mg/day) for 3 years in a double-blind fashion. Patients were stratified at randomization by tumor stage, histology, and smoking status. The primary endpoint (time to SPT) and the secondary endpoints (times to recurrence and death) were analyzed by log-rank test and the Cox proportional hazards model. All statistical tests were two-sided. RESULTS: After a median follow-up of 3.5 years, there were no statistically significant differences between the placebo and isotretinoin arms with respect to the time to SPTs, recurrences, or mortality. The unadjusted hazard ratio (HR) of isotretinoin versus placebo was 1.08 (95% confidence interval [CI] = 0.78 to 1.49) for SPTs, 0.99 (95% CI = 0.76 to 1.29) for recurrence, and 1.07 (95% CI = 0.84 to 1.35) for mortality. Multivariate analyses showed that the rate of SPTs was not affected by any stratification factor. Rate of recurrence was affected by tumor stage (HR for T(2) versus T(1) = 1.77 [95% CI = 1.35 to 2.31]) and a treatment-by-smoking interaction (HR for treatment-by-current-versus-never-smoking status = 3.11 [95% CI = 1.00 to 9.71]). Mortality was affected by tumor stage (HR for T(2) versus T(1) = 1.39 [95% CI = 1.10 to 1.77]), histology (HR for squamous versus nonsquamous = 1.31 [95% CI = 1.03 to 1.68]), and a treatment-by-smoking interaction (HR for treatment-by-current-versus-never-smoking = 4.39 [95% CI = 1.11 to 17.29]). Mucocutaneous toxicity (P<.001) and noncompliance (40% versus 25% at 3 years) were higher in the isotretinoin arm than in the placebo arm. CONCLUSIONS: Isotretinoin treatment did not improve the overall rates of SPTs, recurrences, or mortality in stage I NSCLC. Secondary multivariate and subset analyses suggested that isotretinoin was harmful in current smokers and beneficial in never smokers.

Adult↗

PubMed2001

Serial prostate specific antigen, free-to-total prostate specific antigen ratio and complexed prostate specific antigen for the diagnosis of prostate cancer.

PURPOSE: The free-to-total prostate specific antigen (PSA) ratio and complexed PSA have been introduced as adjuncts to total PSA for prostate cancer screening. Little data exist on the use of these tests for serial PSA screening. We compared serial total PSA, the free-to-total PSA ratio and calculated complexed PSA in men diagnosed with prostate cancer and matched controls in a population based study. MATERIALS AND METHODS: We identified 90 men diagnosed with prostate cancer between 1988 and 1996 with at least 3 serial serum samples obtained at 2-year intervals who were participants in the beta-Carotene and Retinol Efficacy Trial for the prevention of lung cancer. Samples were available up to 10 years before diagnosis. A total of 90 age matched men from the same cohort without prostate carcinoma were identified as controls. Free and total PSA was measured by the Abbott AxSYM system. RESULTS: Baseline demographics of cases and controls were similar. At baseline and diagnosis the men with prostate cancer had higher total and complexed PSA, and a lower free-to-total PSA ratio than controls. Mean followup was 5.2 years in cases and 5.5 in controls. The yearly change in PSA parameters in cases versus controls was 20.7% versus 3.5% for total, -3.4% versus 0.2% for free-to-total and 21.5% versus 3.4% for complexed PSA (p <0.0001). At diagnosis PSA alone was estimated to perform with more than 90% specificity in our model. CONCLUSIONS: In this population based study total PSA was superior to the free-to-total PSA ratio for predicting the development of prostate cancer. While serial changes in free-to-total PSA ratios with time were statistically significantly different in men diagnosed with prostate cancer and controls, the magnitude of these serial changes were slight enough to render them clinically insignificant.

Adenocarcinoma↗

PubMed2001

Predictors of serum selenium in cigarette smokers and the lack of association with lung and prostate cancer risk.

Epidemiological studies have suggested that low levels of selenium are associated with a higher incidence of both lung and prostate cancer. We analyzed the selenium serum concentration in 356 Carotene and Retinol Efficacy Trial (CARET) participants who later developed lung cancer and 356 matched controls and in 235 prostate cancer cases and 456 matched controls. Serum samples were obtained a mean of 4.7 years before diagnosis for both tumor types. Controls were matched to cases by year of randomization, age, smoking status, treatment arm, exposure population (asbestos workers or cigarette smokers), and year of blood draw. In the control population (n = 820), significant predictors of low serum selenium concentration were current smoking status and East Coast locations of the study center. Overall, there was no significant difference in mean serum selenium in lung cancer cases versus controls (11.91 microg/dl versus 11.77 microg/dl) or prostate cancer cases versus controls (11.48 microg/dl versus 11.43 microg/dl). No statistically significant trend in odds ratio was seen across quartiles of serum selenium for lung cancer (P = 0.49) or prostate cancer (P = 0.69). In a subpopulation of 174 prostate cancer patients who had clinical and pathological staging material reviewed, there was no association between serum selenium and Gleason score or clinical or pathological stage. In the CARET population of current and former smokers consuming an ad libitum diet, the serum concentration of selenium was not a risk factor for either lung cancer or prostate cancer.

Age Distribution↗

PubMed2000

Prevention of lung cancer.

Lung cancer is the major cause of death in industrialized western societies. Its link to tobacco abuse is well established and efforts should be made to eliminate this potent environmental carcinogen. The concept of chemoprevention, the use of agents to inhibit and reverse lung cancer carcinogenesis, has great appeal. The CARET study, conducted in 18,000 high-risk smokers in the US, found that a combination of beta-carotene and retinyl palmitate resulted in a 28% increase in the incidence of lung cancer. A similar study conducted in Finland, the ATBC trial utilizing alpha tocopherol and beta-carotene, had similar findings for the group taking beta-carotene. These two trials have caused a rethinking of the use of natural compounds as chemoprevention agents. These agents should no longer be regarded as harmless, but as having potential toxicities. A new approach in the chemoprevention of cancer has been the concept of surrogate endpoints, biological changes that are on the pathway to cancer. Trials are underway to determine what are appropriate surrogate endpoints for lung cancer chemoprevention trials.

Adenocarcinoma↗

PubMed1999

Soluble member(s) of the mesothelin/megakaryocyte potentiating factor family are detectable in sera from patients with ovarian carcinoma.

mAb OV569 was made by immunizing mice with ovarian carcinoma cells. It binds to cells from ovarian carcinomas and, to a lesser extent, to cells from certain other carcinomas whereas the binding to normal tissues is low to nondetectable. It also binds to soluble molecule(s) in culture supernatants from antigen-positive carcinomas. OV569 recognizes a protein(s) of 42-45 kDa with the same N-terminal amino acid sequence as the membrane-bound portion of mesothelin and megakaryocyte potentiating factor (MPF). Binding assays with fusion proteins comprising either the N-terminal part of mesothelin/MPF (D1Ig), reported to be easily cleaved off, or a noncleavable, membrane-associated part (D2Ig) showed that OV569 only binds to D2hIg. A new member of the mesothelin/MPF family was discovered, which has an 82-bp insert in the membrane-associated part, leading to a frameshift of 212 bp, and whose predicted molecular structure indicates that it is soluble. To test patient sera for soluble tumor antigen, antigen was isolated from cell-free tumor culture supernatants via immunoadsorption with OV569 and used to generate murine mAbs to an epitope different from the one to which OV569 binds, after which mAbs to two different epitopes were used to develop a "sandwich ELISA." Using this assay, the level of circulating antigen was elevated significantly in 23 of 30 sera from patients with ovarian carcinoma, as compared with 0 of 68 sera from healthy controls, 0 of 3 sera from patients with nonneoplastic diseases, and 25 of 75 sera from patients with other tumors. Soluble molecules of the mesothelin/MPF family may provide useful new marker(s) for diagnosis of ovarian carcinoma and/or monitoring its response to therapy.

Amino Acid Sequence↗

PubMed1998

Prevention of lung cancer.

Lung cancer chemoprevention continued to make progress in 1997. The incidence of tobacco abuse continues to slowly fall in the United States, and paralleling it, lung cancer incidence. Biomarkers of carcinogenesis and susceptibility continue to be an important area in identifying high-risk patients. The analyses of two major lung cancer prevention trials, beta-Carotene and Retinol Efficacy Trial (CARET) and Alpha-Tocopherol Beta-Carotene (ATBC), were also published this past year. Both found an increased incidence of lung cancer in individuals receiving beta-carotene. In both trials, heavy smokers seem to be the most adversely affected group. The mechanism of this increased incidence of cancer and total deaths still eludes investigators.

Animals↗

PubMed1998

Strategies for recruitment to a population-based lung cancer prevention trial: the CARET experience with heavy smokers. Beta-Carotene and Retinol Efficacy Trial.

The Beta-Carotene and Retinol Efficacy Trial tested the effect of the combination of beta-carotene (30 mg) and retinyl palmitate (25,000 units) daily on the incidence of lung cancer in high-risk individuals. In study centers located in Seattle, WA; Portland, OR; and Irvine, CA, we recruited current and recent ex-cigarette smokers, aged 50-69 years. Our primary method of recruitment was by mailing study information and eligibility questionnaires to age-selected health insurance subscribers. A total of 1,216,549 subscriber households were contacted, which resulted in 16,449 enrollments and 12,184 randomizations. Other methods of recruitment yielded 1421 enrollments and 1002 randomizations. Seventy-four % of those participants who enrolled in the 3-month placebo run-in were randomized. The major reasons for nonrandomization once subjects were enrolled were: becoming ineligible (13%), concern about or development of side effects attributed to the study vitamins (18%), loss of interest or being too busy (23%), and not showing up at the appointed time or not willing to come to the study center (23%). Here, we discuss the reasons for nonparticipation and for subjects leaving the trial prior to randomization and possible modifications of trial design and procedures to address these problems. This recruitment approach provided a constant flow of potentially eligible participants, screened out many ineligible and uninterested persons prior to the scheduling of a study center visit, and ensured randomization of committed participants. A major limitation of this study was that the pool of minorities that was reached was small.

Aged↗

PubMed1997

The clinical evaluation of cancer prevention agents.

The clinical development of cancer chemoprevention agents is similar to that of cytotoxic agents. On the basis of promising preclinical studies, agents with potential efficacy are introduced to the clinic as a phase I trial to study the dose-toxicity relationship of the agent and its human pharmacology. If doses projected to have biological activity have acceptable side effects, the agent proceeds to a phase II trial, which enrolls a larger number of participants and administers the agent for a longer time period (up to 5 years). Phase IIb trials test the effect of these agents on potential biomarkers of carcinogenesis to get some indication if the agent has activity. The phase II trial also pilots study design, mechanisms of recruitment, and adherence for future phase III trials. The phase III trial of a chemopreventive agent determines its effect on cancer incidence. Close attention is also paid to long-term side effects. The unique features of cancer prevention agents and their evaluation must be considered in this stepwise clinical evaluation. These features include (i) populations recruited to prevention trials are healthy; (ii) in this population there is a low tolerance for side effects; and (iii) the clinical end point of the trial, cancer, is statistically an uncommon event. The evaluation of beta-carotene and retinol as studied in the Carotene and Retinol Efficacy Trial (CARET) is used to illustrate this stepwise clinical development.

Anticarcinogenic Agents↗

PubMed1996

Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial.

BACKGROUND: Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in beta-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an alcohol chemical form of vitamin A), and people having higher serum beta-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate). Promptly after the January 18, 1996, announcement that the CARET active intervention had been stopped, we published preliminary findings from CARET regarding cancer, heart disease, and total mortality. PURPOSE: We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the intervention. METHODS: CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for beta-carotene concentration. An Endpoints Review Committee evaluated endpoint reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were estimated by use of Cox regression models; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. O'Brien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 alpha value, and all P values were derived from two-sided statistical tests. RESULTS: According to CARET's pre-specified analysis, there was an RR of 1.36 (95% confidence interval [CI] = 1.07-1.73; P = .01) for weighted lung cancer incidence for the active intervention group compared with the placebo group, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol intake has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum beta-carotene concentrations. CONCLUSIONS: CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland.

Anticarcinogenic Agents↗

PubMed1996

Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease.

BACKGROUND: Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo. RESULTS: A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years. CONCLUSIONS: After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

Aged↗

PubMed1996

The association between participant characteristics and serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol among participants in the Carotene and Retinol Efficacy Trial (CARET) for prevention of lung cancer.

As part of the multicenter Carotene and Retinol Efficacy Trial (CARET) lung cancer prevention study, we investigated the associations of baseline demographic, health history, and nutritional intake information and the prerandomization serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol in a random subset of 1182 smokers and asbestos-exposed workers. Dietary intake was estimated via a self-administered food frequency questionnaire using the recently updated United States Department of Agriculture/National Cancer Institute database. In multiple regression analyses, supplemental vitamin use was the strongest predictor of each of the four analytes. There was a statistically significant inverse relationship between smoking and beta-carotene concentrations. Lower serum beta-carotene was associated with current smoking, higher daily cigarettes smoked, and more pack-years. Serum beta-carotene concentrations were higher with increasing years since stopping cigarette use, which suggests a biological mechanism for the lower serum concentration of beta-carotene in smokers. We found weak inverse associations between alcohol intake and the serum concentrations of both beta-carotene and retinol. As in previous reports, dietary intakes as measured by a food frequency questionnaire can only moderately predict serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol.

Alcohol Drinking↗

PubMed1994

Long-term vitamin A does not produce clinically significant hypertriglyceridemia: results from CARET, the beta-carotene and retinol efficacy trial.

Retinol and retinyl palmitate in the moderate doses tested in chemoprevention trials produce only a negligible increase in serum triglyceride levels. The effect is nonprogressive and is not associated with the kind of exaggerated response reported for interacting factors such as presence of diabetes mellitus and/or high baseline values for serum triglyceride concentration. These findings seem to represent an advantage for safety of retinol in relation to isotretinoin (13-cis-retinoic acid).

Female↗

PubMed1993

Cancer prevention: chemoprevention vs dietary modifications.

BACKGROUND: The goal of cancer chemoprevention research is to identify agents which can reverse or arrest the process of carcinogenesis. Dietary supplementation with a specific agent or micro- or macronutrient has advantages over dietary manipulation. RESULTS: Prescribing a specific "pill" or supplement for long-term daily administration can lead to improved adherence over a behavior or dietary modification. Preclinical studies and clinical trials exploring pharmacokinetics, dose-response relationships, side effects, and ultimately efficacy are greatly facilitated when the agent of interest is defined. The discovery of new agents based on structure/activity relationships and mechanisms of action can be facilitated when an active agent is identified. The primary disadvantage of developing a drug as a cancer prevention agent is the potential for side effects. If active, the agent has the potential to be given to large unmonitored populations over prolonged periods of time. Any agents causing a significant increase in morbidity or mortality for whatever cause, may be more of a liability than an asset from a public health standpoint. CONCLUSION: Whether chemoprevention ultimately turns out to be a dietary constituent, a modification of a naturally occurring substance, or a synthetic compound, the recommendations for use will be based on side effect profile, dose-response, and convenience.

Anticarcinogenic Agents↗

PubMed1993

Phase I trial of chimeric (human-mouse) monoclonal antibody L6 in patients with non-small-cell lung, colon, and breast cancer.

We report a single institution phase I trial of chimeric (mouse-human) monoclonal antibody (chL6) directed against a tumor-associated cell surface antigen expressed in non-small cell lung, colon, and breast cancer. The results of the study were contrasted with a previous trial of murine L6. ChL6 was administered intravenously to 18 patients with advanced cancer as a single, 4-16 infusion in doses ranging from 350 mg/m2 to 700 mg/m2. One patient received four weekly doses of 350 mg/m2. Patients were followed for side effects, localization of antibody to tumor cells, pharmacokinetics and the development of antibodies against chL6. Side effects associated with treatment were chills, fever, and nausea, which lasted 24-48 hours. Platelet count and absolute leukocyte count fell immediately after treatment, but returned to pretreatment levels by day 7. Localization of chL6 to tumor cells in vivo was seen at 350 mg/m2 and "saturation" at 700 mg/m2 and 350 mg/m2 per week x 4. The pharmacokinetics of this antibody appeared similar to its murine analogue. Human antibodies against chL6 were detected in only 4 of 18 patients. These antibodies were directed against murine variable regent and their titers were lower than those occurring in most patients who received murine L6 in an earlier trial. No tumor reductions were seen. Chimeric L6 appears to be a suitable antibody for delivering anti-tumor agents because of its low immunogenicity and favorable in vivo tumor binding characteristics.

Adult↗

PubMed1993

Statistical design and monitoring of the Carotene and Retinol Efficacy Trial (CARET).

CARET is a chemoprevention trial of beta-carotene and vitamin A with lung cancer as the primary outcome. Participants at high risk for lung cancer are drawn from two populations: asbestos-exposed workers and heavy smokers. The intervention is a daily combination of 30 mg beta-carotene and 25,000 IU vitamin A as retinyl palmitate. Nearly 18,000 participants will be followed for a mean 6 years, yielding over 100,000 person-years of follow-up. We project that this sample size will have 80% power to detect a 23% decrease in the incidence of lung cancer cases. The purpose of this paper is to present the values of the key sample size parameters of CARET; our schemes for monitoring CARET for sample size adequacy, incidence of side effects, and efficacy of the study vitamins; an overview of the data collected; and plans for the primary, secondary, and ancillary analyses to be performed at the end of the trial. These approaches to the design, monitoring, and analysis of CARET are applicable for many other prevention trials.

Aged↗

PubMed1993

Chemoprophylaxis strategies in high-risk groups with an emphasis on lung cancer.

The incidence of lung cancer in the United States has stabilized in recent years, but it remains a major cause of death in the United States. Whereas the single most effective primary prevention of this disease would be to eliminate tobacco use from society, this is currently an unrealistic goal. Secondary prevention, however--that is, chemoprophylactic treatment of smokers, exsmokers, and others at risk--represents a viable option. Agents proven effective in both laboratory models and humans include vitamin A and its synthetic derivatives, the retinoids and the carotenoids. It is fairly easy to identify patients at risk of lung cancer compared with other cancers. Yet aside from patients who are under a physician's care and aware of their risk, it can be difficult to target individuals for chemoprophylactic treatment, especially those who are healthy but at high risk and not seeing a physician or other health care provider. Screening for the presence of predictive cellular and molecular changes may facilitate more accurate selection of individuals for chemoprophylactic treatment.

Aged↗