Current concepts in radiation enteritis and implications for future clinical trials

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Abstract
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 β1 (TGF‐β1) leads to increased fibrosis and, ultimately, organ failure. Interferon gamma (IFN‐γ) inhibits the effects of TGF‐β1 in the nucleus. The fibrotic process may be reverted by IFN‐γ in various pathologic conditions. CONCLUSIONS Radiation enteritis and other radiation‐induced, long‐term complications are characterized by excessive stimulation of TGF‐β1. Preliminary studies suggest that IFN‐γ may be effective in the treatment of patients with radiation‐induced cutaneous fibrosis. IFN‐γ should be considered in Phase I–II studies to assess its toxicity and efficacy in the treatment of patients with radiation enteritis. Cancer 2002;95:1151–63. © 2002 American Cancer Society. DOI 10.1002/cncr.10766