Progesterone improves survival in hepatoma cachexia rat model

Background: Medroxyprogesterone (MPA) and megestrol acetate (MA) are synthetic progesterone derivates. Progestagen is an approved drug for cancer cachexia in the USA and some Europe. These agents have been described to increase appetite and to lead to weight gain. However, the effects on survival are still unknown. The aim of this study was to evaluate the effects of progesterone on survival, cardiac function as well as appetite and body weight in the Yoshida hepatoma AH‐130 rat cancer cachexia model. Methods: In this study the effects of progesterone were tested in cachectic tumor bearing rats. Rats were treated with 0.5, 5 or 50mg/kg/d, respectively or placebo daily, starting one day after tumor inoculation for a period of 16 days. Cardiac function was analyzed by echocardiography at baseline and at day 11. Food intake was assessed before tumor inoculation and at day 11. Body weight and body composition were evaluated at the beginning and the end of study or day of euthanasia. Results: Survival was significantly improved by 5 mg/kg/d (HR: 0.48, 95%CI: 0.24‐0.95, p=0.0356). However, there was no significant difference between the progesterone treatment groups compared to placebo in body weight change and body composition, as well as food intake on day 11. Cardiac function also showed no significant difference compared to placebo. Conclusion: Progesterone improves survival, but has no beneficial effects on cardiac function, body weight and food intake in this aggressive hepatoma cancer cachexia rat model. Further studies are needed to elucidate the mechanism of the survival benefit.