CRA7004 Background: Selenium was reported to have possible lung cancer chemopreventive benefits based on a large skin cancer trial secondary observation. (JAMA 1996; 276: 1957-1963). Since that time, research continued to suggest that Se could decrease risk of second primary tumor (SPT) in persons with resected NSCLC. In 2007, a publication from another group suggested an increased association of Se with type 2 diabetes (Annals Int Med 147:217-223). Methods: From Oct 2000-Nov 2009, 6 groups, led by ECOG, carried out a double blind, placebo controlled trial using selenized yeast 200 micrograms daily in a 2:1 randomization vs. placebo for 48 mo in completely resected stage I NSCLC. Participation was 6–36 mo post-op and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, a negative chest x-ray, and no other evidence of recurrence. Planned size of 1,960 participants had been designed to detect a 40% decrease in SPTs with 80% power. Methylation studies of sputum and blood (S. Belinsky) add important biologic correlates to this project. Results: Interim analysis occurred in Oct 2009 after 1,561/1,772 pts reached step 2 (completion of the 4 week (step 1) run-in period requiring at least 75% of the study drug to be taken). Endpoints included SPTs, recurrence, and toxicity. A total of 216 SPTs developed of which 84 (38.9%) were lung cancer. SPT (lung/overall) incidence was 1.36/3.66 per 100 person yrs for placebo vs. 1.91/4.11 for Se (p=.150). 5 yr progression free survival was 78% for placebo vs. 72% for Se. Study was stopped according to futility analysis. Grade 1 or 2 toxicity occurred in 38% of placebo and 39% Se. Grade 3 toxicity was 3% placebo vs. <1% Se. Compliance was excellent (>95% at 2 yrs). Conclusions: No increase in diabetes mellitus or skin cancer was detected. Se was safe but conferred no benefit over placebo. Methylation studies are continuing. [Table: see text]

A mathematical model was developed to predict the outcome of early detection clinical trials or programs targeted at evaluating mortality benefit from earlier diagnosis of breast cancer. The model was applied to eight randomized breast cancer trials, which were carried out to evaluate the benefits of mammography, physical examination or their combination. The model assumes that breast cancer is a progressive disease and any mortality benefit from earlier diagnosis is generated from a favorable shift in the stage at diagnosis relative to usual care. The model predicted the reduction in mortality for seven of the eight trials within the reported confidence intervals. Input data required by the models are: stage shift distribution, examination schedules, population age distribution, follow up time, and survival conditional on stage at diagnosis. Survival distributions were obtained from the 1973-82 SEER database whereas the remaining data was obtained for each of the trials. Information on sensitivity and stage was ordinarily available during the early phase of the trials. The theoretical model has the promise of being able to predict the long-term outcome of early detection trials or programs during the initial examination phase. The theoretical model is general and may be applied to other chronic diseases, which satisfy the basic assumptions.

No abstract