The Beta-Carotene and Retinol Efficacy Trial: Incidence of Lung Cancer and Cardiovascular Disease Mortality During 6-Year Follow-up After Stopping -Carotene and Retinol Supplements
Top Cited Papers
- 30 November 2004
- journal article
- clinical trial
- Published by Oxford University Press (OUP) in JNCI Journal of the National Cancer Institute
- Vol. 96 (23) , 1743-1750
- https://doi.org/10.1093/jnci/djh320
Abstract
The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the effect of daily beta-carotene (30 mg) and retinyl palmitate (25,000 IU) on the incidence of lung cancer, other cancers, and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure. CARET was stopped ahead of schedule in January 1996 because participants who were randomly assigned to receive the active intervention were found to have a 28% increase in incidence of lung cancer, a 17% increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group. After the intervention ended, CARET participants returned the study vitamins to their study center and provided a final blood sample. They continue to be followed annually by telephone and mail self-report. Self-reported cancer endpoints were confirmed by review of pathology reports, and death endpoints were confirmed by review of death certificates. All statistical tests were two-sided. With follow-up through December 31, 2001, the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 (95% confidence interval [CI] = 0.97 to 1.31) and 1.08 (95% CI = 0.99 to 1.17), respectively. Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up. By contrast, the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped. During the post-intervention phase, females had larger relative risks of lung cancer mortality (1.33 versus 1.14; P = .36), cardiovascular disease mortality (1.44 versus 0.93; P = .03), and all-cause mortality (1.37 versus 0.98; P = .001) than males. The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant. Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females, and cardiovascular disease mortality primarily to females and to former smokers.Keywords
This publication has 27 references indexed in Scilit:
- Incidence of Cancer and Mortality Following α-Tocopherol and β-Carotene SupplementationJAMA, 2003
- Stopping the active intervention:Controlled Clinical Trials, 2003
- Cancer Statistics, 2003CA: A Cancer Journal for Clinicians, 2003
- CHEMOPREVENTION OF LUNG CANCER: The Rise and Demise of Beta-CaroteneAnnual Review of Public Health, 1998
- -Tocopherol and beta-Carotene Supplements and Lung Cancer Incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: Effects of Base-line Characteristics and Study ComplianceJNCI Journal of the National Cancer Institute, 1996
- Risk Factors for Lung Cancer and for Intervention Effects in CARET, the Beta-Carotene and Retinol Efficacy TrialJNCI Journal of the National Cancer Institute, 1996
- Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovascular DiseaseNew England Journal of Medicine, 1996
- The Effect of Vitamin E and Beta Carotene on the Incidence of Lung Cancer and Other Cancers in Male SmokersNew England Journal of Medicine, 1994
- Statistical design and monitoring of the carotene and retinol efficacy trial (CARET)Controlled Clinical Trials, 1993
- Can dietary beta-carotene materially reduce human cancer rates?Nature, 1981