Cancer-related cachexia and oxidative stress: beyond current therapeutic options

Cancer-related anorexia/cachexia syndrome is a complex phenomenon in which metabolic abnormalities, proinflammatory cytokines produced by the host immune system, circulating tumor-derived catabolic factors, decreased food intake and probably additional unknown factors all play different roles. This review examines the mechanisms of cancer-related anorexia/cachexia syndrome and the mainstays of its management. The two major options for pharmacological therapy have been progestational agents and corticosteroids. Agents currently under investigation are nonsteroidal anti-inflammatory drugs, N-3 fatty acids, branched-chain amino acids and thalidomide. On the basis of several previously published studies and clinical experience, an innovative treatment approach, which consists of an integrated nutritional and pharmacological treatment, has been developed. This approach, based upon multiple components each targeted at different factors involved, may be effective in both improving objective clinical symptoms, such as lean body mass, and subjective symptoms such as quality of life. A Phase II study has been initiated and Phase III study designed.