Chemoprevention of Lung Cancer

“Hypothesis-driven chemoprevention of lung cancer, when put to the test of randomized large-scale clinical trials, so far has been disappointing, unlike important successes with selective estrogen receptors modulators for breast cancer and non steroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for colon cancer“ (1 ). This somewhat pessimistic statement reflects the outcome of several clinical trials that examined whether human lung cancer could effectively be prevented by dietary supplements. One such agent was beta carotene. In several epidemiological studies negative associations between estimated intakes of vitamin A or of beta carotene (provitamin A) and the risk of developing cancer at various sites seemed to provide compelling reasons for the use of beta carotene as a chemopreventive agent (2 ). Preclinical studies with in vitro and in vivo studies looked promising. However, in large-scale clinical trials it was discovered that in active smokers, beta carotene not only failed to protect, but actually increased the lung cancer risk. The effect was so obvious that one of the clinical trials had to be halted before its scheduled end. When the experimental data base on the chemopreventive action of beta carotene was re-examined, it was found that no really convincing experiments had shown that beta carotene would interfere with tumor development in the respiratory tract. It was pointed out eventually that preclinical studies should evaluate putative chemopreventive agents not just in any system, but in animal models that would approximate the human tumor (3 ).