A randomized double-blind controlled trial: impact of probiotics on diarrhea in patients treated with pelvic radiation

Background & aims: Radical radiation therapy is commonly used for treatment of pelvic cancer. Up to 80% of patients receiving radiotherapy will develop acute radiation induced diarrhea. The primary aim of this randomized double blind controlled trial is to evaluate the effect of the probiotic Bifilact(®) on moderate and severe treatment-induced diarrhea during pelvic radiation.

Methods: Patients with pelvic cancers were treated between 2006 and 2010 at L'Hôtel-Dieu de Québec, University Health Center. Some patients had surgery before pelvic radiotherapy and some received chemotherapy. A total of 246 Patients were randomized between a placebo and either of two regiments of double strain Bifilact(®) probiotics (Lactobacillus acidophilus LAC-361 and Bifidobacterium longum BB-536): a standard dose twice a day (1.3 billion CFU) or a high dose three times a day (10 billion CFU). Patients were trained to record their digestive symptoms daily with a standardized scale and they met a registered dietician and radiation oncologist every week during treatment. The main analysis compared time to first appearance of grade ≥2-3-4 diarrhea using Kaplan-Meier curves as measured by proportion of patients without moderate and severe diarrhea.

Results: 229 patients were analyzed. The difference between the groups for overall grade 2-3-4 diarrhea was not statistically significant (p = 0.13). However at 60 days, the proportion of patients without moderate and severe diarrhea in the standard dose group (35%) was more than twice as high as that of the placebo group (17%) with a hazard ratio of 0.69 (p = 0.04). In patients who had surgery, the standard probiotics dose group had a better proportion of patients without very severe diarrhea than the placebo group, respectively 97% and 74% (p = 0.03). In all groups, the average number of bowel movements per day during treatment was less than 3 soft stools (p = 0.80) and the median abdominal pain less than 1 based on the National Cancer Institute scale (p = 0.23).

Conclusion: Standard dose of Bifilact(®) may reduce radiation induced grade 2-3-4 diarrhea at the end of the treatment of patients with pelvic cancer. In patients operated on before RT, a standard dose of probiotics may reduce radiation induced grade 4 diarrhea. Nutritional interventions by a registered dietician seemed to reduce global digestive symptoms.

Trial registration: clinicaltrials.gov. Identifier NCT01839721.