Table 3. National Cancer Institute's Common Terminology Criteria for Adverse Events: Nausea and Vomitinga continued...
While the optimal dose of octreotide has not been determined, a panel of experts has recommended that complicated cases of diarrhea be managed with intravenous (IV) fluids, octreotide at a starting dose of 100 to 150 μg subcutaneously (SC) 3 times a day or 25 to 50 μg/hour IV with a dose escalation to 500 μg 3 times a day, and administration of antibiotics. This regimen continues until the patient has been diarrhea free for 24 hours. Particularly when patients are receiving chemotherapy, additional evaluation includes 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 is also 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 are 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 µg 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 µg every 8 hours. If the patient presents with severe diarrhea (grade 3 or 4), octreotide, 500 to 1,500 µg SC or IV every 8 hours, may be given as 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.)