Scientists have identified a biomarker for measuring the success of lung cancer chemoprevention, an emerging frontier in the fight against this disease that has long been stymied by a lack of measureable outcomes. These study results were presented at the AACR 102nd Annual Meeting 2011, held April 2-6.

Paul Bunn, M.D., executive director of the International Association for the Study of Lung Cancer and the James Dudley endowed professor of lung cancer research at the University of Colorado Cancer Center at the University of Colorado School of Medicine, said measurements of endobronchial dysplasia, abnormal cell development that can lead to lung cancer, could predict how well a chemoprevention agent is working.

Prostacyclin supplementation by either genetic overexpression or the oral prostacyclin analogue iloprost prevents development of lung cancer in a variety of murine models, including cigarette smoke exposure.

A multi-centre, double-blind, placebo controlled, phase II trial of iloprost was carried out in subjects at increased risk for lung cancer. Subjects were current or former smokers (> 20 pack years); at least mild cytologic atypia on sputum cytology; no previous history of cancer. Subjects were then randomized to oral iloprost (in escalating doses) or placebo. Of the 152 subjects enrolled, 125 completed the pre and post bronchoscopies (60/75 iloprost, 65/77 placebo). Treatment groups were well matched for age, tobacco exposure and baseline histology.

Endobronchial histology was scored within patients to see the change in the two biopsies. 74% of subjects had at least one biopsy displaying mild dysplasia (score 4.0) or worse on the initial bronchoscopy. Baseline histology was significantly worse for current smokers than former smokers. Former smokers receiving oral iloprost exhibited a significant improvement in their post treatment biopsy, and an improvement in dysplasia).

No histologic improvement occurred in current smokers. Proliferation by Ki-67 index was a secondary endpoint and demonstrated no change with iloprost administration. Taken together the results indicate that oral iloprost significantly improves endobronchial dysplasia in former smokers and deserves further study to determine if it can prevent the development of lung cancer. 

"We told people to quit smoking and they did, but half of our lung cancer cases in the United States are coming from people who are former smokers," Bunn said. "We need to work on ways to repair their lungs through chemoprevention."

Bunn analyzed the effect of iloprost among those who had endobronchial dysplasia at enrollment, and found a significant difference in prevalence of endobronchial dysplasia. Moreover, when they analyzed the effect of iloprost on Ki-67, a measure of cell proliferation, the difference was not significant.

This is an important advancement for the chemoprevention field, Bunn said, because it shows that they can test agents, like iloprost, and measure the effect on endobronchial dysplasia as an outcome. Chemoprevention is a goal for cancer researchers, and many of them liken the idea to heart disease prevention with statins, a major public health advance of the past 50 years.

"The challenge is there has been no real equivalent to cholesterol with cancer. This study shows that endobronchial dysplasia could play that role," he said.


Source: AACR 

Watch an ecancertv interview with Dr Paul Bunn