Efficacy of ghrelin in cancer cachexia: clinical trials and a novel treatment by rikkunshito.

Cachexia is characterized by decreased food intake, increased energy expenditure, and muscle wasting. It is observed in 80% of patients with advanced-stage cancer and is a major source of decreased quality of life and increased morbidity and mortality in cancer patients. Ghrelin plays an important role in stimulating hunger and maintaining energy homeostasis and is the first-line treatment option for cancer cachexia. Several studies in rodent models and clinical trials have demonstrated that ghrelin or ghrelin receptor (GHS-R) agonists are effective in the treatment of cancer cachexia; however, further large-scale long-term clinical trials are needed to confirm sustained effects. Recently, the traditional Japanese medicine rikkunshito has been shown to increase food intake in rats with cancer or administered chemotherapeutics. The orexigenic effect of rikkunshito is involved in the stimulation of endogenous ghrelin secretion by blocking the serotonin (5-HT) 2b/2c receptor pathway and the enhancement of GHS-R activity. A potentiator of ghrelin signaling such as rikkunshito may represent a novel approach for the treatment of cancer cachexia.