ORLANDO – Endobronchial dysplasia appears useful as a biomarker for measuring the success of lung cancer chemoprevention, investigators reported at the annual meeting of the American Association for Cancer Research.
Bronchoscopies, along with biopsies of standard endobronchial sites and any other abnormal appearing areas, were performed at baseline and at 6 months after randomization to treatment with iloprost (Ventavis) or placebo in a phase II chemoprevention trial involving 152 former or current smokers with at least a 20 pack-year history.
Paul Bunn, Jr.
Former smokers who received iloprost, an oral prostacyclin analog approved for the treatment of primary pulmonary hypertension, had significant improvements on several measures of endobronchial dysplasia, while current smokers had no improvement, Dr. Paul Bunn reported.
The findings demonstrate that iloprost, which has been shown to prevent the development of lung cancer in various murine models involving cigarette-smoke exposure, also might have the same effect in humans and thus deserves further study for this purpose, Dr. Bunn and his coauthors concluded.
The results also demonstrate that endobronchial dysplasia could serve as a biomarker for effectiveness of chemopreventive treatment– much as cholesterol does in patients being treated with statins to prevent cardiovascular disease, according to Dr. Bunn, executive director of the International Association for the Study of Lung Cancer. He is also the James Dudley endowed professor of lung cancer research at the cancer center at the University of Colorado, Aurora.
In the current study, baseline histology was significantly worse in current smokers than in former smokers (average biopsy scores of 3.0 vs. 2.1, respectively, with a score of 4 indicating mild dysplasia). Former smokers experienced a 0.41-point improvement in average biopsy score (P = .010), a 1.10-point improvement in their worst baseline biopsy score (P = .002), and a 12.5% improvement in dysplasia index (P = .006), which was the percentage of biopsies with a score of at least 4, said Dr. Bunn.
"The histologic improvement in the treated patients who were former smokers was larger than the magnitude of the difference between current and former smokers," he said.
For example, the baseline dysplasia index in current and former smokers was 46% and 31%, respectively, but the pre- and post-treatment dysplasia index in former smokers was 43% and 19.6%, respectively.
Study participants had an average 30 pack-year history of smoking, and at least mild cytologic atypia on sputum cytology, but no previous history of cancer. Iloprost was given in escalating doses across the 6-month treatment period and was well tolerated. The treatment and placebo groups were well-matched for age, tobacco exposure and baseline histology, and there was no difference in dropout rate or serious adverse events between the treatment and placebo groups, Dr. Bunn noted.
Although antismoking campaigns are working – and about half of all smokers have quit, those who quit remain at greater risk for developing lung cancer than are nonsmokers; about half of all cases of lung cancer are in former smokers, and it is important to find effective chemopreventive measures for these individuals, he said.
Dr. Bunn discussed off-label use of iloprost for chemoprevention of lung cancer. He had no other disclosures.