Osterlund, P., Ruotsalainen, T., Korpela, R., Saxelin, M., Ollus, A., Valta, P., … Joensuu, H. (2007). Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer: A randomised study. British Journal of Cancer, 97(8), 1028–1034.

To assess the effect of Lactobacillus and fiber supplementation on tolerability of treatment with chemotherapy containing 5-fluorouracil (5-FU) and to compare the tolerability and frequency of diarrhea with the Mayo regimen (bolus 5-FU) to that of the simplified de Gramont regiment (bolus plus continuous 5-FU)

Postoperative colorectal cancer (CRC) patients were randomly assigned to receive adjuvant chemotherapy monthly (Mayo regimen) or twice monthly (simplified de Gramont regimen) for 24 weeks. Further randomization determined whether patients received the probiotic Lactobacillus rhamnosus GG gelatin capsules twice daily and daily fiber on cycle days 7–14 for 8 days per month during the 24 weeks of chemotherapy. All patients received dietary counseling and kept nutrition diaries. Treatment-related adverse effects were assessed at every cycle.

• The study reported on 148 patients.
• Median age was 60 years, with a range of 31–75.
• The sample was 49% female and 51% male.
• Patients were scheduled to receive adjuvant chemotherapy after surgery for Dukes’ B or C CRC or chemotherapy following surgery for Dukes’ D CRC who were rendered free from metastases by the surgery.

The study was conducted at a single-site, outpatient setting in Finland.

All patients were undergoing the active treatment phase of care.

This was a prospective, randomized trial.

The National Cancer Institute of Canada Common Toxicity Criteria, version 2, was used.

• Less grade 3-4 diarrhea occurred in patients receiving Lactobacillus supplementation than in those not receiving it (22% versus 37%; p = 0.027). 
• Less abdominal discomfort (flatulence, borborygmi, or abdominal distention) of any grade occurred in patients receiving Lactobacillus than in those not receiving it (59% versus 75%; p = 0.058). 
• Only 21% of the patients receiving Lactobacillus had chemotherapy dose reductions due to bowel toxicity as compared to 47% of those who did not receive this supplement (p = 0.0008). 
• Lactobacillus supplementation had no significant effects on overall treatment toxicity or on the frequency of stomatitis or neutropenia.
• Fiber supplementation did not affect overall gastrointestinal (GI) toxicity (p = 0.13).

The frequency of grade 3 or 4 diarrhea and the frequency of abdominal discomfort may be decreased with the use of Lactobacillus rhamnosus supplementation for patients receiving 5-FU-based chemotherapy.

• Adjuvant chemotherapy for CRC now commonly includes irinotecan, capecitabine, or oxaliplatin.  5-FU was the only adjuvant chemotherapy given in this study.
• The study was neither placebo-controlled nor blinded to the administration of the fiber or Lactobacillus.
• Metoclopramide and 5-HT₃ inhibitors were used to treat nausea and vomiting. These medications could possibly have effected reported bowel toxicity.
• No mention was made regarding whether patients were instructed to avoid yogurts and other dairy products produced by fermentation.
• Use of antimicrobials was not mentioned as an exclusion criterion.

The administration of Lactobacilus rhamnosus GG may decrease the frequency and severity of diarrhea and abdominal discomfort with 5-FU-based chemotherapy. Further placebo-controlled, blinded studies are needed.