Kozelsky, T.F., Meyers, G.E., Sloan, J.A., Shanahan, T.G., Dick, S.J., Moore, R.L., … North Central Cancer Treatment Group. (2003). Phase III double-blind study of glutamine versus placebo for the prevention of acute diarrhea in patients receiving pelvic radiation therapy. Journal of Clinical Oncology, 21(9), 1669–1674.

The study design was based on a goal of 120 patients, so that the two-sided, 0.05-level Wilcoxon rank sum would have a power of 97.5% to detect an improvement in diarrhea severity. After stratification, patients were randomly assigned to the experimental group (4 grams of glutamine twice per day for 7 days per week during radiation and for 2 weeks thereafter) or an identically appearing placebo (glycine) for the same time period.

• The study reported on 129 patients from 14 institutions.
• Patients were stratified by
  • History of anterior resection of the rectum versus no prior rectal surgery
  • Total planned cumulative radiation dose
  • Use of fluorouracil (FU)
  • Primary tumor site (rectal versus prostate versus gynecological versus other).

This was a two-arm, placebo-controlled, randomized clinical trial.

The primary measure of treatment efficacy was diarrhea levels, which were evaluated using a bowel function questionnaire that was derived from previous studies on radiation therapy and bowel functioning. Participants completed the questionnaire weekly for 4 weeks, then at 12- and 24-month follow-up intervals. Toxicity was measured using National Cancer Institute (NCI) Common Terminology Toxicity Criteria for Adverse Events: Diarrhea.

No significant differences were found in incidence of diarrhea (p = 0.99), stools per day, maximum stools per day, antidiarrheal agent used, or use of loperamide.

• This study was inconsistent with other studies which found a significant effect (improvement) in diarrhea with glutamine supplementation. Further research is needed to determine whether a lower dose of glutamine was used in this study.
• The authors did not report on the validity or reliability of the bowel function questionnaire.
• No dose-response data was provided to assess whether higher doses or longer pretreatment use of glutamine would have been more effective in treating or preventing diarrhea.