Iloprost May Prevent Lung Cancer in Former Smokers
BY CRAIG GUILLOT
Elsevier Global Medical News
NEW ORLEANS — The oral prostacyclin analogue iloprost showed signs it could prevent some lung cancer in a study of 152 longtime current and former smokers.
Prostacyclin has proved to prevent lung cancer in mice. Authors of the current study, presented at an international conference of the American Thoracic Society, confirmed that oral doses of the drug can significantly improve dysplasia in former smokers.
The phase II clinical trial began with 71 former smokers and 81 current smokers, each with more than 20 pack-years of tobacco exposure. Subjects had to have at least mild sputum cytologic atypia and no previous history of cancer.
The researchers performed autofluorescence and white light bronchoscopy on each participant and biopsies of six standard endobronchial sites. These were scored 1-8 by World Health Organization criteria, where 1 is normal and 8 represents invasive cancer. Endobronchial histology was ranked in patients by three measures: worst biopsy score (Max), dysplasia index (DI), and the average of all biopsy scores (Avg).
Subjects were randomized to oral iloprost or a placebo in escalating doses for 6 months. A second fluorescent bronchoscopy was then performed along with a repeat biopsy of all the central airway areas sampled at the beginning of the study. The follow-up bronchoscopy was performed on 65 study participants in the placebo group and 60 in the iloprost group. Reasons for dropping out were ineligibility, toxicity, and refusal of further treatment.
Among former smokers, those in the oral iloprost group showed significant improvement on all histologic measures, while former smokers receiving placebo showed declines. For the former smokers getting iloprost, the changes were 0.41 better in Avg, 1.1 points better in Max, and 11.6% better in DI than among those getting placebo. Current smokers did not show any such improvement in the drug or placebo groups.
The most common adverse effects exhibited in the original 75 members of the iloprost group included headache, flushing, and nausea.
The trial was led by Dr. Robert Keith of the Denver Veterans Affairs Medical Center and the University of Colorado, Denver. He has been testing several drugs to prevent lung cancer, and his disclosures included financial relationships with Pfizer and Boehringer-Ingelheim.
“This was the first study to show improvement, and I think this will ultimately go to a phase III trial and will involve people that are at the absolute highest risk” of lung cancer, Dr. Keith said. “I think we can now work closely with [the National Cancer Institute] to say that prevention is viable.”
Iloprost is approved in inhaled forms to treat scleroderma, pulmonary hypertension, and Raynaud’s phenomenon. The drug is marketed under the brand name Ventavis by Swiss drug maker Actelion and also comes in an intravenous form called Ilomedin.
Dr. W. Michael Alberts, FCCP, comments
Very few chemoprevention studies have shown benefit. This positive phase II study of oral iloprost in former smokers with dysplasia is encouraging. Let’s hope that subsequent studies confirm the beneficial results.
