Chemoprevention of lung cancer

Our plain-English summary of Chemoprevention of lung cancer, by S.E. Benner, S.M. Lippman, W.K. Hong (Chest, 1995).

The study

• Authors: S.E. Benner, S.M. Lippman, W.K. Hong
• Journal: Chest
• Published: 1995;107(6 Suppl):316S-321S
• Type of article: Review
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Treatment of lung cancer remains frustrating. Most patients with lung cancer are not candidates for curative therapy, and new therapies have not made a substantial impact on survival. Consequently, some clinical investigators have focused their efforts on developing prevention strategies. Chemoprevention, the administration of agents to block or reverse carcinogenesis, is being investigated in ongoing trials. Studies of chemoprevention in lung cancer have included trials to reverse premalignant lesions such as sputum atypia or squamous metaplasia of the bronchial epithelium. Clinical trials of lung cancer prevention have often studied groups of participants with tobacco or asbestos exposure. Other clinical trials are being conducted among patients who have been treated for an early-stage lung cancer. As the result of diffuse epithelial injury, these patients are at very high risk for developing second primary tumors, predominantly in the lungs and upper aerodigestive tract. It is our hope that these studies may establish a new strategy for preventing lung cancer.

In plain English

This 1995 article was a review, not a new study. The authors, from the M.D. Anderson Cancer Center in Houston, described published and ongoing trials of chemoprevention (giving drugs to block or prevent invasive cancer) for lung cancer. Trials aimed at preventing a first lung cancer often enrolled smokers or people with occupational asbestos exposure. These included pilot studies among asbestos-exposed workers for the Carotene and Retinol Efficacy Trial, which tested beta-carotene and retinyl palmitate. That trial was still ongoing, and no results were given. Among the reviewed results, a Finnish trial of 29,133 male smokers found more lung cancers among men given beta-carotene (474 cases) than among men not given it (402 cases). In two placebo-controlled trials, retinoids did not improve precancerous changes in sputum or airway lining more than placebo did. In a trial of patients treated for head and neck cancer, 4% of 49 given 13-cis-retinoic acid and 24% of 51 given placebo developed second primary tumors. The authors concluded that chemoprevention remained experimental.

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: Narrative review of published and ongoing lung cancer chemoprevention trials (no new data collected by the authors)
• Who was studied: Participants in the reviewed trials: smokers, asbestos-exposed workers, and patients previously treated for early-stage lung cancer or head and neck cancer
• Exposure: Chemoprevention agents tested in the reviewed trials: retinoids (13-cis-retinoic acid, etretinate, retinyl palmitate, 4-HPR), beta-carotene, alpha-tocopherol, folate with vitamin B12, and N-acetylcysteine. The trial populations had tobacco or asbestos exposure; no asbestos fiber types or doses were given.
• Main results:
  • Finnish trial of 29,133 male smokers: lung cancer incidence was higher among those who received beta-carotene (474 cases) than among those who did not (402 cases), p=0.01
  • Randomized trial by Heimburger et al (73 evaluable patients): the trial's authors believed folate and vitamin B12 were associated with greater improvement in sputum cytology than placebo. The review notes these results had not been duplicated.
  • Randomized trial of etretinate vs placebo in 150 smokers (Arnold et al): no difference in sputum atypia between the groups
  • French phase 2 study of etretinate in 40 heavy smokers: the metaplasia index fell from 34.57 to 26.96% among participants who continued smoking (p less than 0.001)
  • M.D. Anderson randomized trial of 13-cis-retinoic acid vs placebo (69 participants completed): the metaplasia index fell from 35.8 to 28.1% for all participants, with no further improvement from the retinoid
  • Head and neck cancer trial (Hong et al): 4% of 49 patients treated with 13-cis-retinoic acid vs 24% of 51 placebo-treated patients developed second primary tumors (p=0.005)
  • Retinyl palmitate trial after resection of stage I non-small cell lung cancer (Pastorino et al, 307 patients): 18 patients in the treated group vs 29 in the observation group developed a second primary tumor
  • The Carotene and Retinol Efficacy Trial, whose pilot studies included asbestos-exposed workers, was described as ongoing with no results reported
• The authors' conclusion: The authors concluded that chemoprevention was being actively studied but remained experimental. They expressed hope that ongoing studies would show a reduction in cancer incidence.
• Limitations the authors state:
  • Changes in biomarkers such as premalignant lesions would have to be validated in studies using cancer incidence as the end point before conclusions could be drawn
  • The beta-carotene finding in the Finnish trial could be the result of chance

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, Carcinogenesis, Sputum, Epithelium, Clinical Trial, Asbestos Exposure.

Related studies

• Chemoprevention or antichemoprevention? A salutary warning From the beta-carotene experience — M. Paolini, S.Z. Abdel-Rahman, et al. (2001)
• 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)
• 'Natural' cancer prevention trial halted — K. Peterson (1996)
• The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements — G.E. Goodman, M.D. Thornquist, et al. (2004)
• Modulation of genotoxic and related effects by carotenoids and vitamin A in experimental models: mechanistic issues — S. De Flora, M. Bagnasco, et al. (1999)
• Beta-Carotene, vitamin A, and lung cancer chemoprevention: results of an intermediate endpoint study — J.W. McLarty, D.B. Holiday, et al. (1995)

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