The iloprost lung cancer chemoprevention study was a multicenter, phase II, randomized, double-blind, placebo-controlled trial of iloprost in subjects at increased risk for lung cancer (defined as current or former smokers with 20 pack year or more smoking history, at least mild sputum cytologic atypia, or a history of biopsy proven endobronchial dysplasia). The majority of subjects were recruited from pulmonary medicine clinics. Exclusion criteria included prior history of cancer, significant comorbid disease or inability to undergo 2 bronchoscopies, hypoxemia with the required use of supplemental oxygen, use of inhaled steroids within 6 weeks of trial enrollment, and carcinoma in situ or invasive cancer on endobronchial biopsy. Sputum was collected and cytology was graded by a single cytopathologist (W. A. Franklin) as previously published (18 (link)). Autofluorescence and/or white light bronchoscopy was carried out before randomization and after 6 months of treatment, with 6 standard endobronchial sites biopsied (all were carini, identified as RUL, RML, RB6, LUL, LUDB, and LB6), along with all other visually suspicious appearing areas.
The trial sample size was 152 subjects and, after obtaining written informed consent, participants were block randomized based on smoking status (current vs. former) and study center. The randomization sequence was generated prior to trial initiation and stored in a password-protected spreadsheet accessible only to the trial biostatistician and study administrator. Subjects were randomized only after confirmation of eligibility, and blinding was maintained throughout the trial. Following randomization, subjects were started on either iloprost or placebo at an initial dose of 1 tablet BID (50 μg iloprost clathrate per tablet). The subjects had a monthly clinical evaluation and if well tolerated, iloprost or placebo was dose escalated by 1 tablet monthly to a maximum dose of 3 tablets BID. Following 6 months of treatment, a second bronchoscopy was carried out with repeat biopsies at all of the baseline sites. Adverse events were monitored and reported twice yearly to an independent data and safety monitoring board (DSMB). A final clinical visit occurred 1 month after completing the trial and subjects are currently undergoing passive follow-up (i.e., yearly questionnaires). The trial involved 7 clinical centers (listed in theAppendix ) funded by the National Cancer Institute as the Lung Cancer Biomarkers and Chemoprevention Consortium and individual site SPORE grants. The institutional review boards at each study center approved the study protocol. This trial was listed and registered on ClinicalTrials.gov (Identifier: NCT00084409). Bayer-Schering Pharma AG (Berlin) provided the study medication and placebo tablets.
The trial sample size was 152 subjects and, after obtaining written informed consent, participants were block randomized based on smoking status (current vs. former) and study center. The randomization sequence was generated prior to trial initiation and stored in a password-protected spreadsheet accessible only to the trial biostatistician and study administrator. Subjects were randomized only after confirmation of eligibility, and blinding was maintained throughout the trial. Following randomization, subjects were started on either iloprost or placebo at an initial dose of 1 tablet BID (50 μg iloprost clathrate per tablet). The subjects had a monthly clinical evaluation and if well tolerated, iloprost or placebo was dose escalated by 1 tablet monthly to a maximum dose of 3 tablets BID. Following 6 months of treatment, a second bronchoscopy was carried out with repeat biopsies at all of the baseline sites. Adverse events were monitored and reported twice yearly to an independent data and safety monitoring board (DSMB). A final clinical visit occurred 1 month after completing the trial and subjects are currently undergoing passive follow-up (i.e., yearly questionnaires). The trial involved 7 clinical centers (listed in the
