A randomized double blind placebo controlled multicenter study of mesalazine for the prevention of acute radiation enteritis

• Published in: Radiotherapy and oncology 1997-07, Vol.44 (1), p.59-63
• Main Authors: Resbeut, Michel, Marteau, Philippe, Cowen, Didier, Richaud, Pierre, Bourdin, Sylvain, Dubois, Jean Bernard, Mere, Pascale, N'Guyen, Tan D.
• Format: Article
• Language: English
• Subjects: Acute Disease; Acute radiation enteritis; Adult; Aged; Aminosalicylic Acids - therapeutic use; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Diarrhea - drug therapy; Double-Blind Method; Enteritis - drug therapy; Female; Humans; Male; Mesalamine; Mesalazine; Middle Aged; Pelvic irradiation; Pelvis - radiation effects; Radiation Injuries - drug therapy; Radiotherapy - adverse effects
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/S0167-8140(97)00064-9

Background and purpose: Symptoms of acute radiation enteritis (ARE), dominated by diarrhea, occur in more than 70% of patients receiving pelvic irradiation. Eicosanoids and free radicals release have been implicated in the pathogenesis. Mesalazine (5-ASA) is a potent inhibitor of their synthesis in the mucosa and could therefore be of some interest in preventing ARE. Patients and methods: The study was performed in six radiotherapy units in France who agreed on standardized irradiation procedures. One hundred and fifty-three patients planned for external beam radiotherapy to the pelvis ≥45 Gy for prostate ( n = 97) or uterus ( n = 54) cancer were randomized on a double blind basis to receive prophylactic 5-ASA (4 g/day Pentasa ®) or placebo. Patients with concomitant chemotherapy were excluded. Prostate and uterus cancers were chosen since these centropelvic tumors require a similar radiotherapy protocol during the first step of treatment and involve a comparable volume of small intestine. The symptoms of ARE and their severity were assessed every week during irradiation, and 1 and 3 months after its end. All patients followed a low fiber and low lactose diet. End points were diarrhea, use of antidiarrheal agents, abdominal pain, and body weight. Effficacy was evaluated using intention to treat. Results: (means ± SD) Groups did not differ for age (mean 64 ± 9 years), sex, tumor site, or irradiation procedure. During irradiation, diarrhea occurred in 69% and 66% of the 5-ASA and placebo groups, respectively ( χ 2, P = 0.22). Curves of survival without diarrhea did not differ between groups (logrank P = 0.09). Severity of diarrhea did not differ between groups except at d15 where it was significantly more severe in the 5-ASA group (ANOVA P = 0.006). Duration of diarrhea did not differ (22 ± 15 days in both groups, P = 0.88). Abdominal pain was less frequently reported in the 5-ASA group at d28 (34% vs. 51%, P = 0.048). Use of antidiarrheal agents and body weight did not differ between groups. Conclusion: Mesalazine 4 g/day did not decrease the symptoms of ARE.