THE CAROTENE AND RETINOL EFFICACY TRIAL (CARET) TO PREVENT LUNG-CANCER IN HIGH-RISK POPULATIONS - PILOT-STUDY WITH CIGARETTE SMOKERS

In preparation for a phase IV lung cancer chemoprevention trial, we co nducted a pilot trial of beta-carotene and retinol in high-risk smoker s. 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 q uit 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 interve ntion arms: placebo, retinol, 25,000 international units/day; beta-car otene, 30 mg/day; or retinol plus beta-carotene. Participants were fol lowed for side effects and adherence every 2 months either by a teleph one call or a clinic visit. Blood was sampled for retinoid, carotenoid , and liver function analyses annually. Beta-carotene 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 b oth beta-carotene arms. No differences were seen among arms or over ti me in incidence or severity of the other 15 monitored symptoms and sig ns or in serum liver function tests. Adherence was good: 83% of partic ipants remained active on study at 1 year and 75% at 2 years. Serum be ta-carotene increased from a prerandomization median concentration of 170 to 2100 ng/ml after 4 months of supplementation, and retinyl palmi tate median levels more than tripled. Results from this pilot study le d to streamlining of the safety monitoring protocol, decisions on agen ts and dosage, and refinement of study design parameters for the multi center Carotene and Retinol Efficacy Trial (CARET).