The role of intervention studies in ascertaining the contribution of dietary factors in lung cancer. The Seattle chemoprevention trial of retinoids in asbestos-exposed workers

Our plain-English summary of The role of intervention studies in ascertaining the contribution of dietary factors in lung cancer. The Seattle chemoprevention trial of retinoids in asbestos-exposed workers, by G.S. Omenn, G.E. Goodman, G.D. Kleinman, et al (Annals of the New York Academy of Sciences, 1988).

The study

• Authors: G.S. Omenn, G.E. Goodman, G.D. Kleinman, L. Rosenstock, S. Barnhart, P. Feigl, D.B. Thomas, D. Kalman, B. Lund, R.L. Prentice
• Journal: Annals of the New York Academy of Sciences
• Published: 1988;534:575-83
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 003868).

Summary of the article

This paper described the design of the Seattle chemoprevention trial, which tested whether oral retinoids could reduce lung cancer and mesothelioma in asbestos-exposed workers, and discussed problems of prevention trials. Eligible subjects were aged 45 to 74. They had either at least 15 years since first asbestos exposure and a positive chest X-ray by ILO criteria, or 5 years' work in a high-risk trade in the Pacific Northwest, such as pipefitting, insulating or shipyard work. Subjects were located through workers' compensation systems, the U.S. Navy Asbestos Medical Surveillance program at Bremerton, medical specialists, lawyers and union screening programs. The planned double-blind randomized trial required about 2500 subjects (1250 per arm) receiving 25,000 units of retinol plus 15 mg of beta-carotene daily, or placebo. Subjects completed a 2-month run-in period and were stratified by smoking status, time since first exposure and chest X-ray result. The endpoints were the incidences of lung cancer and mesothelioma. From data reported by Berry and by Selikoff and Hammond, the authors estimated a lung cancer risk of 10 per 1000 person-years in the placebo group. They calculated that, allowing for 20 percent attrition over 5 years, a 40-50 percent reduction could be detected with 80 percent power. All of the first 36 subjects met the run-in compliance criterion. The authors noted that prevention trials differ from treatment trials in endpoints, duration, sample size, dosing strategy and logistics; almost 10 million capsules would be needed. They concluded that drug-based chemoprevention was a useful approach complementing primary prevention, but that its logistic complications and costs needed to be appreciated and streamlined.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This article described the design of the Seattle chemoprevention trial. It was a planned double-blind randomized trial of whether daily retinol (25,000 units) plus beta-carotene (15 mg) could reduce lung cancer and mesothelioma in asbestos-exposed workers. The article reported no cancer results. Eligible people were aged 45 to 74. They needed 15 years since first asbestos work exposure, and either a chest X-ray positive by ILO criteria or 5 years' work in a high-risk trade, such as pipefitters, insulators or shipyard boilermakers in the Pacific Northwest. The authors planned about 2500 subjects, 1250 per arm. Allowing for 20 percent attrition over 5 years, they estimated this could detect a 40-50 percent reduction in cancer incidence with 80 percent power (one-sided type I error of 5 percent), assuming a placebo-group lung cancer risk of 10 per 1000 person-years. All of the first 36 subjects met the compliance requirement during a 2-month run-in. The authors also discussed practical difficulties of prevention trials. They concluded that using specific drugs seemed a useful experimental approach, but that the logistic complications and costs needed to be appreciated and streamlined.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Description of the design and rationale of a planned double-blind, randomized, placebo-controlled chemoprevention trial; no outcome results reported
• Who was studied: A planned 2500 or so asbestos-exposed workers aged 45 to 74 in the Pacific Northwest (Seattle). They needed 15 years since first asbestos work exposure, and either a chest X-ray positive by ILO criteria or 5 years' work in a known high-risk trade. Subjects were stratified as 15-30 or 30+ years since first exposure. They were recruited through compensation systems, the U.S. Navy surveillance program, physicians, lawyers and union screening programs. 36 subjects were enrolled at the time of writing.
• Exposure: Asbestos exposure, shown by radiographic evidence of asbestos-related lung disease or by work in high-risk trades (pipefitters, steamfitters, shipyard boilermakers, insulators, shipyard electricians, shipscalers, plasterboard workers). The intervention was 25,000 units of retinol plus 15 mg of beta-carotene daily, compared with placebo.
• Main results:
  • The planned sample of 2500, allowing for 20 percent attrition over 5 years, was estimated to detect a 40-50 percent reduction in cancer incidence with 80 percent power, using a one-sided type I error of 5 percent
  • Subjects in the placebo group were estimated to face a lung cancer risk of 10 per 1000 person-years. This was a planning assumption, not an observed result.
  • For planning, the authors reanalyzed published tabulated data on insulation workers. Among those who had reached 20 years since first exposure at the start of the 10-year follow-up, the rates were 11 per 1000 for lung cancer and 6 per 1000 for mesothelioma.
  • All of the first 36 subjects met the run-in compliance criterion of an average of five or more daily doses per week for 2 months
  • Almost 10 million capsules would be needed for 2500 subjects over 5 years. Drug supply accounted for more than a year's delay in starting the project.
• The authors' conclusion: The authors concluded that using specific drugs, rather than changing dietary intake, seemed a useful experimental approach, but that the logistic complications and costs needed to be appreciated and streamlined.
• Limitations the authors state:
  • A lower incidence in the untreated group, a smaller sample or lower efficacy would reduce statistical power
  • The comparison cohorts used to estimate risk probably had higher exposures than the trial's subjects
  • The blood assay used to monitor compliance cannot detect a few missed doses

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Mesothelioma, Asbestos Exposure, Chest X-Ray.

Related studies

• Retinoids in lung cancer chemoprevention and treatment — S. Toma, P. Raffo, et al. (1999)
• Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial — G.S. Omenn, G.E. Goodman, et al. (1996)
• Chemoprevention of cancer: lessons to be learned from beta-carotene trials — H. Vainio (2000)
• CARET, the beta-carotene and retinol efficacy trial to prevent lung cancer in asbestos-exposed workers and in smokers — G.S. Omenn, G. Goodman, et al. (1991)
• Protective dietary factors and lung cancer — E.T. Fontham (1990)
• Recruitment for the beta-carotene and retinol efficacy trial (CARET) to prevent lung cancer in smokers and asbestos-exposed workers — G.S. Omenn, G. Goodman, et al. (1992)

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