Previous studies animal and phase I/II studies suggested that regular ATP infusions may inhibit loss of body weight in cancer. In this report, we summarize data from a recent trial (Agteresch et aL [2000a] J Natl Cancer Inst 92:321-328; Agteresch et al. [2000b] Eur J Clin Pbarmacol 56:49-55) in 58 patients with non-small-cell lung cancer, stage IIIB or IV. Patients were randomized to receive either 10 intravenous 30-h ATP infusions every 2 to 4 weeks (n = 28), or no ATP (n - 30). Body weight, body composition (anthropometry, isotope dilution), muscle strength (elbow flexor and knee extensor), energy intake (3-day food record), and quality of life (validated Rotterdam Symptom Checklist, RSCL) were assessed at 4-week intervals during 28 weeks. Between-group differences were tested for statistical significance (P <0.05) by repeated-measures analysis of covariance. Over the 28-week follow-up period, the control group showed progressive deterioration in body weight, fat mass, body cell mass, arm muscle area, and elbow flexor and knee extensor muscle strength. In contrast, in the ATP group, complete stabilization of these parameters was observed. Energy intake decreased significantly in the control group, but remained stable in the ATP group. ATP also inhibited the progressive rise in plasma values of C-reactive protein seen in control patients. All mentioned between-group differences were statistically significant. Significant favorable effects of ATP were also found for different domains of quality of life as assessed by the RSCL, i.e., physical, functional, and overall quality of life, whereas no significant effect of ATP on the psychological subscale of the RSCL was detected. In conclusion, ATP is the first agent that has been shown, in a randomized clinical trial, to counteract the loss of both metabolically active tissues (skeletal muscle and body cell mass) and fat mass, and improve muscle strength and quality of life (including functional status and fatigue) in patients with advanced cancer. Maintenance of energy intake and inhibition of chronic inflammation are likely to contribute to these effects of ATP. These results warrant further studies in patients with cancer and inflammatory diseases.