Efficacy of probiotics combined with glutamine compound for acute radiation enteritis during neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A randomized controlled trial (NCT05406882).

Abstract

3624 Background: Acute radiation enteritis (ARE) occurs in up to 80% of patients undergoing abdominal-pelvic radiotherapy, with severe ARE causing treatment interruption in 20%. Current prophylactic strategies remain inadequate. Small-sample studies suggest probiotics and glutamine may reduce radiation-induced mucosal injury and intestinal syndrome (e.g., diarrhea), but evidence-based validation is insufficient. This study investigated the efficacy of probiotics combined with glutamine compound preparation in preventing and alleviating ARE in locally advanced rectal cancer (LARC) patients receiving chemoradiotherapy. Methods: This prospective randomized trial enrolled 176 stage II-III rectal adenocarcinoma patients receiving preoperative chemoradiotherapy, randomized 1:1 to prophylactic (group A, n=86) versus therapeutic (group B, n=84) (treatment started when patients had ≥ 2° ARE) administration of probiotics combined with glutamine compound. Concurrent chemoradiotherapy consisted of pelvic radiation 50-50.4 Gy/25-28 fractions plus oxaliplatin/capecitabine. Weekly assessments documented ARE (including anal tenesmus/pain, diarrhea, constipation, hematochezia) basing on RTOG and CTCAE v5.0 criteria. Primary endpoints: incidence of grade ≥2 ARE and diarrhea. Chi-square or Fisher's exact tests were used for analysis through R version 4.4.2. P<0.05 indicated statistical significance. Results: The enrollment was completed on August 5, 2025. Six patients withdrew consent (group A: 1; group B: 5). Ultimately, there were 170 patients who completed concurrent chemoradiotherapy (84 control, 86 treatment), including 105 males (61.8%). The incidence rate of ≥ 2° ARE in group A was significantly lower than that in group B (44.2% vs 73.8%, P<0.001; RR=0.60, 95%CI: 0.46-0.78). The incidence rate of ≥ 2° diarrhea was also significantly lower in group A (34.9% vs 54.8%, P=0.01). There was 1.2% (1/86) and 3.6% (3/84) of grade 3 ARE in the two groups, respectively; and all these four patients experienced grade 3 diarrhea. The incidence rate of ≥ 2° ARE increased with higher doses of pelvic radiotherapy in both groups, with the peak incidence occurring in the fifth week (24.1%) of group A and the fourth week (35.7%) of group B, respectively. Conclusions: Prophylactic probiotics combined with glutamine compound has a preventive effect of severe radiation enteritis and diarrhea during concurrent chemoradiotherapy for rectal cancer. Clinical trial information: NCT05406882 .