Giralt, J., Regadera, J. P., Verges, R., Romero, J., de la Fuente, I., Biete, A., … Guarner, F. (2008). Effects of probiotic lactobacillus casei DN-114 001 in prevention of radiation-induced diarrhea: Results from multicenter, randomized, placebo-controlled nutritional trial. International Journal of Radiation Oncology, Biology, Physics, 71(4), 1213–1219.

To determine whether a liquid yogurt containing Lactobacillus casei DN-114 reduces the incidence or the severity of diarrhea in patients with cervical carcinoma receiving radiation therapy with concomitant cisplatin or in patients with postoperative endometrial adenocarcinoma receiving radiation therapy

Patients receiving conventional fractionation pelvic radiation therapy for cervical carcinoma (radiation therapy with weekly cisplatin) or for endometrial adenocarcinoma were randomly assigned to receive 96 mL of fermented liquid containing yogurt with Lactobacillus casei DN-114-001 or the same amount of placebo in 2-mg capsules, three times per day. Loperamide was used as necessary as rescue medication; no other antidiarrheal medications were permitted. Consumption of loperamide was recorded. Patients kept daily diaries.

• The study reported on 85 patients.
• The mean age was 60.91 years (SD = 11.80 years) in the intervention group and 59.34 years (SD = 12.77 years) for the placebo group.
• All of the patients were female.
• Patients had been diagnosed with endometrial adenocarcinoma requiring postoperative pelvic radiation therapy or advanced cervical squamous cell carcinoma requiring pelvic radiation therapy with concomitant weekly cisplatin.
• Patients had European Cooperative Oncology Group (ECOG) performance statuses of less than 2.
• Patients were excluded from the study if they
  • Had other types of pelvic tumors.
  • Were receiving treatment with chemotherapy agents other than cisplatin.
  • Had received prior chemotherapy or radiation therapy.
  • Were being treated with antimicrobials or immunosupressors at inclusion.
  • Had experienced any acute or chronic gastrointestinal (GI) condition associated with diarrhea in the month prior to recruitment.

The study was conducted at multiple outpatient settings in Spain.

Patients were undergoing the active treatment phase of care.

This was a placebo-controlled, double-blind, randomized clinical trial in two parallel groups.

The Bristol Stool Scale, National Cancer Institute (NCI) Common Toxicity Criteria (CTC), and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - C30 were used.

• No significant differences were found in
  • Development of grade 2 or worse diarrhea
  • Need for rescue medication (loperamide)
  • Withdrawal because of a lack of efficacy
  • Time to the first occurrence of grade 2 or 3 diarrhea
  • Time to the first occurrence of type 5 (soft) stools (Bristol Scale)
  • Quality-of-life questionnaire scores
  • Complications reported at 6 months.
• The first incidence of type 6 (fluffy) stools (Bristol scale) was significantly shorter in the placebo group (median of 10 days) than in the intervention group (median of 14 days, (p = 0.048).
• No adverse events were considered related to the study product.

The use of a fermented liquid yogurt containing Lactobacillus casei DN-114-001 did not decrease the incidence of radiation-induced diarrhea.

• The sample size was small, with fewer than 100 patients.
• No intent-to-treat analysis was performed.
• Accrual was terminated prematurely because of recruiting difficulties and did not reach calculated sample size to achieve 80% power.
• 5-HT₃ inhibitors were used to treat nausea/vomiting. Because these are associated with constipation, their use could have affected stool consistency.

The probiotic Lactobacillus casei does not appear to decrease the incidence of radiation-induced diarrhea.