Interventions With Adequate Evidence That They Do Not Reduce Risk
Studies have examined whether it is possible to prevent cancer development in the lung using chemopreventive agents. Chemoprevention is defined as the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent carcinogenesis before the development of invasive malignancy. So far, agents tested for efficacy in lung cancer chemoprevention have been micronutrients, such as beta-carotene and vitamin E.
Beta-carotene supplementation in nonsmokers
Two other randomized controlled trials of beta-carotene were carried out in populations that were not at excess risk of lung cancer. The Physicians' Health Study was designed to study the effects of beta-carotene and aspirin in cancer and cardiovascular disease. The study is a randomized, double-blind, placebo-controlled trial begun in 1982 involving 22,071 male physicians aged 40 to 84 years. After 12 years of follow-up, beta-carotene was not associated with overall risk of cancer (RR = 0.98) or lung cancer among current (11% of study population) or former (39% of study population) smokers.
In the Women's Health Study (WHS) approximately 40,000 female health professionals were randomly assigned to 50 mg beta carotene on alternate days or placebo. After a median of 2.1 years of beta-carotene treatment and 2 additional years of follow-up, there was no evidence that beta-carotene protected against lung cancer, as there were more lung cancer cases observed in the beta-carotene (n = 30) than placebo (n = 21) group. The strong evidence from rigorous randomized, placebo-controlled trials clearly indicate that beta-carotene supplementation does not lower the risk of lung cancer in populations that are not high-risk for lung cancer.
Vitamin E supplementation
The Heart Outcomes Prevention Evaluation (HOPE) trial began in 1993 and continued follow-up as the HOPE-The Ongoing Outcomes (HOPE-TOO) through 2003. In this randomized, placebo-controlled trial, patients aged 55 years or older with vascular disease or diabetes were assigned to 400 IU vitamin E or placebo. With a median follow-up of 7 years, the group randomly assigned to vitamin E had a significantly lower lung cancer incidence rate (1.4%) than the placebo group (2.0%) (RR = 0.72; 95% CI, 0.53-0.98). However, the protective association between vitamin E supplements and lung cancer in the HOPE-TOO study needs to be interpreted in the context of evidence from other randomized trials. In the ATBC study, supplementation with alpha-tocopherol produced no overall effect on lung cancer (RR = 0.99; 95% CI, 0.87-1.13). In the WHS of 40,000 female health professionals, using 600 IU of vitamin E every other day showed no evidence of protection against lung cancer in women (RR = 1.09; 95% CI, 0.83-1.44). The Medical Research Council/British Heart Foundation Heart Protection Study (HPS) is a randomized placebo-controlled trial to test antioxidant vitamin supplementation with vitamin E, vitamin C, and beta-carotene among 20,536 United Kingdom adults with coronary disease, other occlusive arterial disease, or diabetes. The trial began recruitment in 1994, and as of the 2001 follow-up the results showed a slightly higher rate of lung cancer in the vitamin group compared with the placebo group (1.6% vs. 1.4%, respectively).