A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED MULTICENTER STUDY OF MESALAZINE FOR THE PREVENTION OF ACUTE RADIATION ENTERITIS

Background and purpose: Symptoms of acute radiation enteritis (ARE), d ominated by diarrhea, occur in more than 70% of patients receiving pel vic irradiation. Eicosanoids and free radicals release have been impli cated 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 s ix radiotherapy units in France who agreed on standardized irradiation procedures. One hundred and fifty-three patients planned for external beam radiotherapy to the pelvis greater than or equal to 45 Gy for pr ostate (n = 97) or uterus (n = 54) cancer were randomized on a double blind basis to receive prophylactic 5-ASA (4 g/day Pentasa(R)) or plac ebo. Patients with concomitant chemotherapy were excluded. Prostate an d 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 an d their severity were assessed every week during irradiation, and 1 an d 3 months after its end. All patients followed a low fiber and low la ctose diet. End points were diarrhea, use of antidiarrheal agents, abd ominal pain, and body weight, Efficacy was evaluated using intention t o treat. Results: (means +/- SD) Groups did not differ for age (mean 6 4 +/- 9 years), sex, tumor site, or irradiation procedure. During irra diation, diarrhea occurred in 69% and 66% of the 5-ASA and placebo gro ups, respectively (chi(2), P = 0.22). Curves of survival without diarr hea did not differ between groups (logrank P = 0.09). Severity of diar rhea did not differ between groups except at d15 where it was signific antly more severe in the 5-ASA group (ANOVA P = 0.006), Duration of di arrhea did not differ (22 +/- 15 days in both groups, P = 0.88). Abdom inal 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 n ot differ between groups. Conclusion: Mesalazine 4 g/day did not decre ase the symptoms of ARE. (C) 1997 Elsevier Science Ireland Ltd.