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Nutritional Modulation of Antitumor Efficacy and Diarrhea Toxicity Related to Irinotecan Chemotherapy in Rats Bearing the Ward Colon Tumor

Authors' Affiliations: Departments of ¹ Oncology and ² Agriculture, Food, and Nutritional Science, and ³ The Center of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, Alberta, Canada

Requests for reprints: Vickie E. Baracos, Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada T6G 1Z2. Phone: 780-432-8232; E-mail: vickieb{at}cancerboard.ab.ca.

Purpose: To evaluate and compare the influence of dietary elements on cancer progression, chemotherapy efficacy, and toxicity, particularly severe, late-onset diarrhea related to irinotecan (CPT-11) treatment.

Experimental Design: We used laboratory rats fed a standardized basal diet, Ward colon tumor, and CPT-11 therapy for the study of CPT-11–induced diarrhea. Dietary interventions were selected from nutrients already established to modify other forms of colitis and which have been hypothesized to mitigate chemotherapy-induced gastrointestinal injury (glutamine, n-3 fatty acids, prebiotic oligosaccharides). Animals adapted to test diets were treated with CPT-11 at the maximum tolerated dose (125 mg/kg x 3 days) and diarrhea was followed continuously for 1 week.

Results: The inclusion of n-3 fatty acids in the diet (5%, w/w of total fat) suppressed tumor growth and enhanced CPT-11's efficacy; this treatment did not affect the incidence or severity of diarrhea. By contrast, oral glutamine bolus (0.75 g/kg) administered prior to each CPT-11 treatment reduced the incidence of severe diarrhea (34.1 ± 4.7% versus 53.8 ± 4.2%, P < 0.005) and decreased the area under the curve of diarrhea score (16.5 ± 1.0 versus 18.8 ± 0.5, P < 0.05). Identical results were obtained with i.v. bolus glutamine administration. Glutamine treatment did not alter CPT-11's antitumor efficacy. The addition of prebiotic oligosaccharides to the diet (8%, w/w of diet) did not mitigate the severity of diarrhea, and it raised the activity of β-glucuronidase in cecal contents, a key bacterial enzyme mediating CPT-11–related intestinal toxicity.

Conclusion: Our experiments suggest that glutamine and n-3 fatty acids might be potentially useful adjuncts to CPT-11 treatment.

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				H. Xue, M. B. Sawyer, C. J. Field, L. A. Dieleman, D. Murray, and V. E. Baracos Bolus Oral Glutamine Protects Rats against CPT-11-Induced Diarrhea and Differentially Activates Cytoprotective Mechanisms in Host Intestine but Not Tumor J. Nutr., April 1, 2008; 138(4): 740 - 746. [Abstract] [Full Text] [PDF]