The effect of oral sucralfate on the acute proctitis associated with prostate radiotherapy: A double-blind, randomized trial

Purpose: Acute rectal complications occur in the majority of patients recei ving external-beam radiotherapy for carcinoma of the prostate. Sucralfate h as been proposed to reduce radiation-induced mucosal injury by forming a pr otective barrier on ulcer bases, binding local growth factors, and stimulat ing angiogenesis. However, there is conflicting clinical evidence as to whe ther sucralfate, taken prophylactically during radiotherapy, can ameliorate the symptoms of acute radiation proctitis. Methods and Materials: A double-blind randomized trial was conducted at fou r Radiation Oncology Departments in Sydney, Australia, between February 199 5 and June 1997. A total of 338 patients with clinically localized prostate cancer receiving small volume radiotherapy, of whom 335 were evaluable, we re randomized to receive either 3 g of oral sucralfate suspension or placeb o twice a day during radiotherapy. Patients kept a daily record of their bo wel symptoms and were graded according to the RTOG/EORTC acute toxicity cri teria. Results: One hundred sixty-four patients received sucralfate and 171 receiv ed placebo. Both groups were well balanced with regard to patient, tumor, t reatment factors, and baseline symptoms, except that the placebo group had a significantly more liquid baseline stool consistency score (p = 0.004). P atients kept a daily diary of symptoms during radiotherapy. After adjusting for baseline values, there was no significant difference between the two g roups with regard to stool frequency (p = 0.41), consistency (p = 0.20), fl atus (p = 0.25), mucus (p = 0.54), and pain (p = 0.73). However, there was more bleeding in the sucralfate group, with 64% of patients noticing rectal bleeding, compared with 47% in the placebo group (p = 0.001). There was no significant difference between the two groups with respect to RTOG/EORTC a cute toxicity (p = 0.88; sucralfate 13%, 44%, 43% and placebo 15%, 44%, 40% for grade 0, 1, and 2, respectively). Conclusion: This study suggests that oral sucralfate taken prophylactically during radiotherapy does not ameliorate the symptoms of acute radiation pr octitis and may increase acute bleeding. The cause of the increased bleedin g in the sucralfate group is unclear. As the pathogenesis of acute and late reactions are different, late follow-up, which includes sigmoidoscopic eva luation, is currently being performed on this cohort of patients. (C) 2001 Elsevier Science Inc.