Probiotics are nutritional supplements that contain a defined amount of viable microorganisms and, upon administration, confer a benefit to the patient. The use of probiotic functional foods (beneficial live microorganisms) to modify gut microflora has been suggested in clinical conditions associated with diarrhea, gut-barrier dysfunction, and inflammatory response. There are a vast number of different strains of probiotics; however, much of the clinical research has investigated the species belonging to the family of Lactobacillus and Bifidobacterium. Probiotics have been promoted for the following:[41,42,43,44,45,46]
- Prevention of antibiotic-induced diarrhea and rotavirus.
- Treatment or prevention of inflammatory bowel disease, irritable bowel syndrome, and gastroenteritis.
- Treatment of necrotizing enterocolitis in premature infants.
The results of one study among adults with cancer have been published. In a double-blind, randomized, controlled trial, 450 adults with cancer who were receiving radiation to the pelvic region were randomly assigned to receive the blend probiotic product VSL #3 or placebo during radiation therapy. The authors reported a decrease in the incidence and severity of diarrhea. No adverse events were reported.
Clinical trials for the following patients are under way:
- Patients with familial adenomatous polyposis (NCT00319007).
- Adults undergoing allogeneic hematopoietic stem cell transplantation (NCT00946283).
- Children and adolescents undergoing allogeneic myeloablative hematopoietic stem cell transplantation (NCT01010867).
While the optimal dose of octreotide has not been determined, a panel of experts has recommended that complicated cases of diarrhea should be managed with intravenous (IV) fluids, octreotide at a starting dose of 100 to 150 ?g subcutaneously (SC) 3 times a day or 25 to 50 ?g/hour IV with a dose escalation to 500 ?g 3 times a day, and administration of antibiotics. This regimen should be continued until the patient has been diarrhea free for 24 hours. Particularly when patients are receiving chemotherapy, additional evaluation should include stool workup (including blood, fecal leukocytes, C. difficile, Salmonella, E. coli, Campylobacter, and infectious colitis), complete blood count, and electrolyte profile. This workup and treatment should also be considered for patients who progress to grade 3 or 4 diarrhea while taking loperamide. The same panel suggests that severe radiation therapy-induced diarrhea may not require hospitalization (an alternative outpatient unit or intensive home care nursing may be able to provide the same level of care and monitoring) but the patient's constellation of symptoms should be considered to determine the appropriate workup and whether IV fluids or octreotide is indicated.
Octreotide, a somatostatin analog, is currently the most promising agent in the management of severe diarrhea caused by a variety of diseases and treatments. The doses used in clinical trials have varied widely. Regardless of the lack of consensus regarding optimal dose, octreotide has been shown to be effective in relieving diarrhea associated with AIDS, carcinoid syndrome, and vasoactive intestinal polypeptide tumors.[Level of evidence: II] Several open-label and randomized controlled studies of octreotide in the relief of chemotherapy-induced diarrhea have demonstrated the efficacy of this therapy.[49,50,51][Level of evidence: I];[52,53,54][Level of evidence: II] In a prospective trial of 32 patients who had chemotherapy-induced diarrhea that was refractory to loperamide, octreotide 100 ?g SC 3 times a day produced complete resolution in 30 patients. Resolution occurred rapidly, with 5 patients responding within 24 hours, 14 patients responding within 48 hours, and 11 patients responding within 72 hours after beginning treatment. No adverse effects of the octreotide were noted. Octreotide has also been shown to be effective in diarrhea associated with GVHD.[56,57] An expert panel recommended using high-dose loperamide (2 mg every 2 hours) for the first day of chemotherapy-induced diarrhea that is low grade (1 and 2), followed by octreotide, 100 to 150 ?g every 8 hours. If the patient presents with severe diarrhea (grade 3 or 4), octreotide, 500 to 1,500 ?g SC or IV every 8 hours, should be first-line therapy. A phase III, double-blind study of depot octreotide for the prevention of diarrhea during pelvic radiation treatment did not demonstrate any benefit. In fact, some gastrointestinal symptoms such as cramping may have been worse. Parenteral hydration and electrolyte supplementation may be indicated, and in severe cases, total parenteral nutrition may be initiated. (Refer to the PDQ summary on Nutrition in Cancer Care for more information.)