Purpose/Objective: Cancer patients are often significantly catabolic, with limited anabolic stimulus (limited nutrient intake, inactivity, low testosterone). Weight loss in cancer is disproportionately lean tissue. Anabolic androgenic steroids increase weight, protein synthesis, and nitrogen retention across a broad spectrum of conditions. The oral anabolic agent, oxandrolone, is a synthetic derivative of testosterone. Intent-to-treat data in a previous open label study of oxandrolone (10 mg bid × 4 months) in 131 weight-losing cancer patients increased weight 2.1% (p<0.02) and body cell mass (BCM, the physiologically active component of lean tissue), 5.3% (p<0.006). Weight gain was associated with improved scores for quality of life and performance status. The purpose of the current study is to confirm the previous results and to compare the safety and efficacy of oxandrolone vs placebo in patients with aerodigestive cancers and weight loss. Materials/Methods: A randomized, double blind, placebo-controlled study (last subject enrolled January 2003) utilized an integrated approach to weight gain including patient education in nutrition and resistance exercise with study drug (oxandrolone 10 mg bid vs placebo) for 4 months. Subjects received customized nutrition education and goals and elasticized exercise bands. Monthly assessment included weight, body composition by bioelectrical impedance analysis, ECOG performance status, quality of life, and laboratory parameters. C-reactive protein was measured as a marker of catabolism. Key inclusion criteria: aerodigestive tract cancer, significant weight loss (active loss or 3% loss in 1 month or 5% loss in 6 months), ECOG performance status of 0–3, and life expectancy of >6 months. Results: Data are preliminary in nature, since data collection for the full four months is ongoing. Data are presented as mean (range). Demographics: n= 64 (43 men, 21 women); race: 48 white, 9 Hispanic, 5 black, 2 other; mean age 66.7 years (47–86). Cancers: 24 lung, 37 head and neck, 3 cervical esophagus. Preliminary blinded analysis of the current data is summarized below. Conclusions: Blinded analysis of preliminary data in a randomized, double blind, placebo-controlled study of oxandrolone 10 mg bid or placebo in weight-losing cancer patients reveals that half of the subjects gained weight and/or lean tissue, while half continued losing after study entry. The last subject enrolled will finish in May. Full unblinded analysis of safety and efficacy of oxandrolone vs placebo, with assessment of predictors of response, will be completed during summer 2003.