Current concepts in radiation enteritis and implications for future clinical trials

BACKGROUND. Radiation enteritis is one of the most feared complications of abdominal and pelvic radiation. Once its occurs, the process is relentless and may result in the patient's death. Available treatment is only supportive. Recent progress in molecular biology has shed some light on the pathogenesis of radiation enteritis and other diseases that are characterized by excessive fibrosis. New treatment modalities may be devised to improve the outcome of patients who are affected with this complication. METHODS. A literature search was used to identify the common denominator between many radiation-induced fibrotic conditions and other sclerotic diseases. Factors that affect the disease process and possible therapeutic interventions were evaluated. RESULTS. The hyperstimulation of transforming growth factor beta1 (TGF-beta1) leads to increased fibrosis and, ultimately, organ failure. Interferon gamma (IFN-gamma) inhibits the effects of TGF-beta1 in the nucleus. The fibrotic process may be reverted by IFN-gamma in various pathologic conditions. CONCLUSIONS. Radiation enteritis and other radiation-induced, long-term complications are characterized by excessive stimulation of TGF-beta1. Preliminary studies suggest that IFN-gamma may be effective in the treatment of patients with radiation-induced cutaneous fibrosis. IFN-gamma should be considered in Phase I-II studies to assess its toxicity and efficacy in the treatment of patients with radiation enteritis.