The Carofene and Retinol Efficacy Trial (CARET) to Prevent Lung Cancer in High-Risk Populations: Pilof Study with Cigarette Smokers

In preparation for a phase IV lung cancer chemoprevention trial, we conducted a pilof trial of β-carofene and retinol in high-risk smokers. Eligibility criteria were ages of 50-69 years, a smoking history of at least 20 pack-years, and either being a current smoker or having quit within the past 6 years. Participants were recruited by mailing an interest survey to 29,928 age-selected members of King County Medical Blue Shield. We randomized 1,029 women and men to one of four intervention arms: placebo, retinol, international units/day; β -carofene, 30 mg/day; or retinol plus β-carofene. Participants were followed for side effects and adherence every 2 months either by a telephone call or a clinic visit. Blood was sampled for retinoid, carofenoid, and liver function analyses annually. β-carofene and retinol were well tolerated during the follow-up period, which had a median of 1.5 years and a maximum of 3.3 years. Yellowing of the skin was seen in bofh β-carofene arms. No differences were seen among arms or over time in incidence or severity of the other 15 monitored symptoms and signs or in serum liver function tests. Adherence was good: 83% of participants remained active on study at 1 year and 75% at 2 years. Serum β-carofene increased from a prerandomization median concentration of 170 to 2100 ng/ml after 4 months of supplementation, and retinyl palmitate median levels more than tripled. Results from this pilof study led to streamlining of the safety monitoring profocol, decisions on agents and dosage, and refinement of study design parameters for the multicenter Carofene and Retinol Efficacy Trial (CARET).