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  • Title: Nutritional modulation of antitumor efficacy and diarrhea toxicity related to irinotecan chemotherapy in rats bearing the ward colon tumor.
    Author: Xue H, Sawyer MB, Field CJ, Dieleman LA, Baracos VE.
    Journal: Clin Cancer Res; 2007 Dec 01; 13(23):7146-54. PubMed ID: 18056195.
    Abstract:
    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 beta-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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