CARET, the beta-carotene and retinol efficacy trial to prevent lung cancer in asbestos-exposed workers and in smokers

Our plain-English summary of CARET, the beta-carotene and retinol efficacy trial to prevent lung cancer in asbestos-exposed workers and in smokers, by G.S. Omenn, G. Goodman, J. Grizzle, et al (Anti-cancer Drugs, 1991).

The study

• Authors: G.S. Omenn, G. Goodman, J. Grizzle, M. Thornquist, L. Rosenstock, S. Barnhart, G. Anderson, J. Balmes, M. Cherniack, J. Cone
• Journal: Anti-cancer Drugs
• Published: 1991;2(1):79-86
• Type of article: Randomized trial
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

CARET is a two-armed, double-blind, randomized chemo-prevention trial to test the hypothesis that oral administration of beta-carotene 30 mg/day plus retinyl palmitate 25,000 IU/day will decrease the incidence of lung cancer in high-risk populations: heavy smokers and asbestos-exposed workers who have smoked. The agents combine anti-oxidant and nuclear tumor suppressor mechanisms. Fastidious monitoring for possible side effects is facilitated by inclusion of a Vanguard population. As of 31 December 1990, 6,105 participants of the 18,000 needed have been randomized in the trial. Efficacy results are expected in 1999.

In plain English

This article described the design of CARET, a randomized, double-blind trial. It tested whether daily beta-carotene (30 mg) plus retinyl palmitate (25,000 IU) would lower lung cancer rates versus placebo. New recruits were heavy smokers and asbestos-exposed workers who had smoked. Participants from 1985–88 pilot studies (816 asbestos-exposed men and 1029 smokers) continued as a Vanguard group; the asbestos pilot had no smoking requirement, and 16% of it had never smoked. Efficacy results were expected in 1999; none were reported. New asbestos-exposed recruits needed extensive exposure starting at least 15 years earlier, plus an ILO-positive chest X-ray and/or at least 5 years in a high-risk trade (such as insulation or shipyard work) completed at least 10 years earlier. The main outcomes tracked were lung cancer and mesothelioma. Pilot doses raised blood vitamin levels without liver toxicity signs or more relevant symptoms, except mild skin yellowing with beta-carotene. As of 31 December 1990, 6,105 of the 18,000 participants needed had been randomized. The authors expected CARET and two other trials to show by decade's end whether these vitamins could be recommended.

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 of a two-armed, double-blind, randomized chemoprevention trial (placebo versus beta-carotene plus vitamin A), with early pilot-study experience; no efficacy results
• Who was studied: Two groups. The Efficacy group was recruited at US centers (Baltimore, New Haven, Portland, San Francisco, Seattle, and Irvine from 1991) since 1989. It included heavy smokers (men and women aged 50–69) and asbestos-exposed men aged 45–69 who were current smokers or had quit within 15 years. The Vanguard group was made up of continuing participants from the 1985–88 Seattle pilot studies: 816 asbestos-exposed men, with no smoking requirement and men up to 74 eligible, and 1029 smokers. By 31 December 1990, 6,105 of 18,000 needed participants had been randomized.
• Exposure: Study treatment: beta-carotene 30 mg/day plus retinyl palmitate 25,000 IU/day, or placebo. Asbestos-exposed participants had to have extensive occupational exposure, with at least 15 years since first occupational exposure. They also needed a chest X-ray positive by ILO criteria and/or at least 5 years in a high-risk trade, completed at least 10 years earlier. Listed trades included insulator, shipyard trades, plasterboard worker, plumber/pipefitter and sheetmetal worker. No fiber type was specified for the trial population.
• Main results:
  • In the pilot studies, the chosen doses raised blood carotene and retinyl palmitate levels. They did so without signs of liver toxicity, a marked rise in triglycerides, or more relevant symptoms or signs, except mild skin yellowing in those on beta-carotene.
  • Pilot randomization during 1985–88: 816 men in the asbestos-exposed cohort (target 800) and 1029 men and women in the smokers pilot (target 920).
  • The asbestos-exposed pilot had no smoking eligibility requirement. Of the pilot asbestos-exposed population, 16% were never-smokers, 62% ex-smokers and 22% current smokers.
  • Including dropouts, adherence to the study vitamins at 3 years after randomization was 80% in the asbestos-exposed workers cohort.
  • The planned primary endpoints were diagnoses of lung cancer or mesothelioma. The secondary endpoints were other cancers and deaths from all causes.
  • The sample-size calculation required over 4000 asbestos-exposed workers and over 13,000 smokers. This gave 80% power to detect a 33% maximal reduction in lung cancer incidence.
• The authors' conclusion: The authors expected CARET, combined with two other major trials, to determine by the end of the decade whether vitamin A and beta-carotene can be recommended as chemopreventive agents against lung cancer.
• Limitations the authors state:
  • The sample-size and power calculations depended on extensive assumptions, some of which were being revised as field experience accumulated.
  • The study's power could be diluted in two ways. Placebo participants might take the vitamins on their own, given the publicity and their presence in multivitamins. Active-arm participants might fail to take their capsules.
  • The trial was not recruiting miners, textile workers, cement product makers, or certain other asbestos-exposed job groups.

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.

Related studies

• 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)
• 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)
• Research cost analyses to aid in decision making in the conduct of a large prevention trial, CARET. Carotene and Retinol Efficacy Trial — M.D. Thornquist, N. Urban, et al. (1993)
• Changes in cholesterol and triglyceride concentrations in the Vanguard population of the Carotene and Retinol Efficacy Trial (CARET) — B. Cartmel, J. Dziura, et al. (2005)
• Lobe of origin and histologic type of lung cancer associated with asbestos exposure in the Carotene and Retinol Efficacy Trial (CARET) — C.A. Brodkin, J. McCullough, et al. (1997)
• Participation and adherence among older men and women recruited to the Beta-Carotene and Retinol Efficacy trial (CARET) — M.D. Thornquist, D.L. Patrick, et al. (1991)

Browse more research in Anti-cancer Drugs, or return to medical research.