Drugs for preventing lung cancer in healthy people

Our plain-English summary of Drugs for preventing lung cancer in healthy people, by M. Caraballoso, M. Sacristan, C. Serra, et al (The Cochrane Database of Systematic Reviews, 2003).

The study

• Authors: M. Caraballoso, M. Sacristan, C. Serra, X. Bonfill
• Journal: The Cochrane Database of Systematic Reviews
• Published: 2003:CD002141
• Type of article: Systematic review
• Cited by: 39 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Some studies have suggested a protective effect of antioxidant nutrients on lung cancer. Observational epidemiological studies suggest an association between higher dietary levels of fruits and vegetables containing beta carotene and a lower risk of lung cancer.

Objectives: To determine whether vitamins, minerals and other potential agents, alone or in combination, reduce incidence and mortality from lung cancer in healthy people.

Search Strategy: The electronic databases MEDLINE (1966-july 2001), EMBASE (1974-july 2001) and the Cochrane Controlled Trial Register (CENTRAL, Issue 3/2001) and bibliographies were searched. In addition authors of included studies were contacted to identify potentially eligible published and unpublished trials.

Selection Criteria: Included studies were randomised controlled clinical trials comparing different supplements or comparing supplements with placebo, administered to healthy people with the aim of preventing lung cancer.

Data Collection And Analysis: Three reviewers independently selected the trials to be included in the review and assessed the methodological quality of each trial, and two extracted data using a standardised form. For each study, relative risk and 95% confidence limits were calculated for dichotomous outcomes.

Main Results: Four studies were eligible for inclusion. All were population based trials, including a total of 109,394 participants. Two studies included smokers, one included workers exposed to asbestos and two studies were carried out in health professionals. A group of participants with no known risk factors for lung cancer was included in the study sample of two trials. Beta-carotene was evaluated in all trials, alone or combination with alpha-tocopherol or retinol, and one study tested alpha-tocopherol alone. Duration of treatment varied from 2 to 12 years and follow-up was from two to five years. All trials had a placebo group. For people with risk factors for lung cancer no reduction in lung cancer incidence or mortality was found in those taking vitamins alone compared with placebo (incidence of lung cancer: RR 0.98, 95% CI 0.81-1.19; lung cancer mortality: RR 0.93, 95% CI 0.73-1.19). For people with no known risk factors of lung cancer, none of the vitamins or their combinations appeared to have any effect. Combined data from three studies showed a non-statistically significant increased risk of lung cancer incidence (RR 1.11, 95% CI 0.94-1.33) and mortality (RR 1.05, 95% CI 0.87-1.28) for beta-carotene alone at pharmacological doses in groups with risk factors for lung cancer. When beta-carotene was combined with retinol, data from a single study showed that there was a statistically significant, increased risk of lung cancer incidence (RR 1.42, 95% CI 1.13-1.80) and mortality (RR 1.75, 95% CI 1.29-2.38) in people with risk factors for lung cancer who took both vitamins compared with those who took placebo. Data from also from one study showed that the combination of beta-carotene with alpha-tocopherol in people with risk factors for lung cancer was associated with a non-statistically significant increased risk of lung cancer incidence (RR 1.16, 95% CI 0.96-1.39) and mortality (RR 1.15, 95% CI 0.91-1.45). No effect was observed for total cancer incidence, mortality or all-cause mortality.

Reviewer's Conclusions: There is currently no evidence to support recommending vitamins such as alpha-tocopherol, beta-carotene or retinol, alone or in combination, to prevent lung cancer. A harmful effect was found for beta-carotene with retinol at pharmacological doses in people with risk factors for lung cancer (smoking and/or occupational exposure to asbestos). More research from larger trials and with longer follow-up is needed to analyse the effectiveness of other supplements.

In plain English

This was a Cochrane systematic review that pooled randomised, placebo-controlled trials testing whether vitamins, minerals or other agents prevent lung cancer in healthy people. Four trials with 109,394 participants were included. They covered smokers, health professionals, and (in the CARET trial) 4,060 male workers exposed to asbestos. The review grouped smokers and asbestos workers together as "high risk." Only vitamins had been tested: beta-carotene, alpha-tocopherol and retinol. In high-risk people, vitamins as a group did not reduce lung cancer. The increases were not statistically significant: incidence RR 1.17 (95% CI 0.97-1.43) and mortality RR 1.25 (95% CI 0.91-1.71). In the single trial giving beta-carotene with retinol, the risk was statistically significantly higher: incidence RR 1.42 (95% CI 1.13-1.80) and mortality RR 1.75 (95% CI 1.29-2.38). No effect was seen on total cancer or all-cause mortality. The authors concluded there was no evidence for recommending these vitamins to prevent lung cancer. They noted that the combined-vitamin results each came from one study, and that no study tested retinol alone.

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: Systematic review and meta-analysis (Cochrane review) of randomised, placebo-controlled trials
• Who was studied: Four trials (ATBC in Finland; CARET, Physicians' Health Study and Women's Health Study in the USA) with 109,394 healthy adults in total. Participants were smokers, health professionals, and 4,060 male asbestos-exposed workers in CARET. Smokers and asbestos-exposed people were analysed together as "high risk." People with no known risk factors were analysed as "low risk."
• Exposure: Vitamin supplements versus placebo. ATBC tested alpha-tocopherol 50 mg daily and beta-carotene 20 mg daily, alone or combined. CARET tested beta-carotene 15 or 30 mg combined with retinol 25,000 IU. The Physicians' Health Study tested beta-carotene 50 mg on alternate days. Asbestos exposure was a basis for classing CARET participants as high risk, not an intervention.
• Main results:
  • High-risk people (smokers and/or asbestos workers; 4 studies, 63,794 people): lung cancer incidence with any vitamins versus placebo was RR 1.17 (95% CI 0.97-1.43). This increase was not statistically significant.
  • High-risk people: lung cancer mortality with any vitamins versus placebo was RR 1.25 (95% CI 0.91-1.71). This was not statistically significant.
  • Low-risk people (non-smokers; 2 studies, 45,524 people): no effect of vitamins on lung cancer incidence (RR 1.04, 95% CI 0.60-1.80).
  • Beta-carotene alone in high-risk groups (3 studies, 30,916 participants): a small increase in lung cancer incidence (RR 1.11, 95% CI 0.94-1.33) that was not statistically significant.
  • Alpha-tocopherol alone (ATBC, 14,573 smokers): no effect on lung cancer incidence (RR 0.98, 95% CI 0.81-1.19) or mortality (RR 0.93, 95% CI 0.73-1.19).
  • Beta-carotene combined with retinol (CARET only; smokers and asbestos-exposed workers): a statistically significant increase in lung cancer incidence (RR 1.42, 95% CI 1.13-1.80) and lung cancer mortality (RR 1.75, 95% CI 1.29-2.38).
  • Beta-carotene combined with alpha-tocopherol (ATBC only; smokers): increases in lung cancer incidence (RR 1.16, 95% CI 0.96-1.39) and mortality (RR 1.15, 95% CI 0.91-1.45) that were not statistically significant.
  • No effect was seen on total cancer incidence, total cancer mortality or all-cause mortality.
• The authors' conclusion: The authors concluded that there was currently no evidence for recommending alpha-tocopherol, beta-carotene, retinol or their combinations to prevent lung cancer in healthy people.
• Limitations the authors state:
  • Little information was available on how treatment allocation was concealed and on how long treatments lasted.
  • Follow-up was relatively short because two trials were stopped early. In the Women's Health Study, treatment lasted a median of only 2.1 years.
  • The results for each vitamin combination (beta-carotene with alpha-tocopherol; beta-carotene with retinol) each came from a single study.
  • It remains uncertain whether the excess risk comes from beta-carotene, retinol or their combination, because no study tested retinol alone.
  • Analysis by duration of treatment could not be done for lack of data.
  • Losses to follow-up were 31% in the ATBC study and 3% in the CARET study.

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, Clinical Trial, Relative Risk, Occupational Exposure.

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