Glutamine for Irinotecan Diarrhea

Savarese, Diane; Al-Zoubi, Ammar; Boucher, Jean

doi:10.1200/jco.2000.18.2.450

Cited by 34 publications

(23 citation statements)

References 8 publications

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“…For some the direct target is the intestinal mucosa, controlling the absorption of electrolytes and water (glutamine, acetorphan and octeotride) or modulating the immune/inflammatory reactions (budesonide, thalidomide, Celecoxib, and JBT 3002 lipopeptide; refs. [28][29][30][31][32][33][34]. Other drugs reduce the endoluminal concentration of active SN-38 by blocking the intestinal carboxylesterase using alkalinization of intestinal lumen, baicaline, or, more significantly, antibiotics (12, 35 -39).…”

Section: Discussionmentioning

confidence: 99%

Intestinal microflora and digestive toxicity of irinotecan in mice.

Brandi

Dabard

Raibaud

et al. 2006

Clinical Cancer Research

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Purpose: Delayed diarrhea is the most important side effect of irinotecan. The aim of this study was to investigate the role of intestinal microflora on the induction of systemic and intestinal toxicity and diarrhea, studying germ-free and holoxenic mice i.p. injected with irinotecan. Experimental Design: To evaluate the lethal dose, starting with 100 mg/kg/4 d, we treated the holoxenic mice with100, 80, and 60 mg/kg/4 d and germ-free mice with 60, 80,100, and150 mg/ kg/4 d. We recorded the percentage of dead animals, diarrhea, and the epithelial damage to the jejunum, ileum, cecum, and colon at optical and scanning electron microscopy. Results: Germ-free mice were more resistant to irinotecan than the holoxenic group. The lethal dose was between 60 and 80 mg of irinotecan for holoxenic mice and z150 mg for the germ-free. The intestinal damage score was higher in holoxenic than germ-free mice at 100 mg and equally diffuse in the small and large bowel. The damage in germ-free mice was less severe (8 of 40 samples) prevailing in the ileum. The differences were significant for all sites (jejunum, P < 0.001; ileum, P = 0.012; cecum, P = 0.001; colon, P < 0.001). No damage was found in germ-free mice at 60 mg. Diarrhea was present in all 100 and 80 mg holoxenic mice and in 19 of 20 cases at 60 mg whereas it was absent in 60 mg or sporadic in 80 and 100 mg germ-free mice. Conclusions: The intestinal microflora plays a key role in the intestinal toxicity of irinotecan.

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Section: Discussionmentioning

confidence: 99%

Intestinal microflora and digestive toxicity of irinotecan in mice.

Brandi

Dabard

Raibaud

et al. 2006

Clinical Cancer Research

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“…In recent years, several attempts have been made to prevent irinotecan-induced delayed-type diarrhea in humans [22,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. Most strategies have focused on intervening in its metabolic pathway to reduce SN-38 concentrations in the gut.…”

Section: Introductionmentioning

confidence: 99%

Prophylaxis of Irinotecan-Induced Diarrhea with Neomycin and Potential Role for ***UGT1A1*28*** Genotype Screening: A Double-Blind, Randomized, Placebo-Controlled Study

et al. 2006

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Objective. Delayed-type diarrhea is a common side effect of irinotecan and is associated with a bacterialmediated formation of the active irinotecan metabolite SN-38 from its glucuronide conjugate in the intestine. Based on a pilot study, we hypothesized that concomitant administration of the antibiotic neomycin would diminish exposure of the gut to SN-38 and ameliorate the incidence and severity of diarrhea.Patients and Methods. Patients were treated with irinotecan in a multicenter, double-blind, randomized, placebo-controlled trial. Eligible patients received irinotecan (350 mg/m 2 once every 3 weeks) combined with neomycin (660 mg three times daily for three consecutive days, starting 2 days before chemotherapy) or combined with placebo. Blood samples were obtained for additional pharmacokinetic and pharmacogenetic analyses.Results. Sixty-two patients were evaluable for the toxicity analysis. Baseline patient characteristics, systemic SN-38 exposure, and UGT1A1*28 genotype status (i.e., an additional TA repeat in the promoter region of uridine diphosphate-glucuronosyltransferase isoform 1A1) were similar in both arms. Although distribution, severity, and duration of delayed-type diarrhea did not differ significantly between arms, grade 3 diarrhea tended to be less frequent in the neomycin arm. The presence of at least one UGT1A1*28 allele was strongly related to the incidence of grade 2-3 diarrhea. In the neomycin arm, grade 2 nausea was significantly more common.Conclusion. Our results do not suggest a major role for neomycin as prophylaxis for irinotecaninduced delayed-type diarrhea. It is suggested that the UGT1A1*28 genotype status could be used as a screening tool for a priori prevention of irinotecan-induced delayedtype diarrhea. The Oncologist 2006;11:944-954

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“…Reduction in intestinal absorption and increase in permeability were significantly greater in the placebo arm (P ¼ .02), while the incidence of diarrhea and use of loperamide tablets was decreased in the glutamine patients (P ¼ .09 and P ¼ .002, respectively). A small case series (n ¼ 6) showed benefit using a proprietary oral glutamine product in metastatic colon cancer patients who had irinotecan-induced diarrhea unresponsive to loperamide and severe enough to require the suspension of therapy [139]. All patients restarted on chemotherapy with the addition of 10 g of glutamine three times a day beginning the day before irinotecan infusion and continuing until 4 days afterwards were able to tolerate full doses of chemotherapy.…”

Section: Intestinal Toxicitymentioning

confidence: 99%

Dietary Supplement Use in Cancer Care: Help or Harm

Hardy

2008

Hematology/Oncology Clinics of North America

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Glutamine for Irinotecan Diarrhea

Cited by 34 publications

References 8 publications

Intestinal microflora and digestive toxicity of irinotecan in mice.

Intestinal microflora and digestive toxicity of irinotecan in mice.

Prophylaxis of Irinotecan-Induced Diarrhea with Neomycin and Potential Role for ***UGT1A1*28*** Genotype Screening: A Double-Blind, Randomized, Placebo-Controlled Study

Dietary Supplement Use in Cancer Care: Help or Harm

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Glutamine for Irinotecan Diarrhea

Cited by 34 publications

References 8 publications

Intestinal microflora and digestive toxicity of irinotecan in mice.

Intestinal microflora and digestive toxicity of irinotecan in mice.

Prophylaxis of Irinotecan-Induced Diarrhea with Neomycin and Potential Role for UGT1A1*28 Genotype Screening: A Double-Blind, Randomized, Placebo-Controlled Study

Dietary Supplement Use in Cancer Care: Help or Harm

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Prophylaxis of Irinotecan-Induced Diarrhea with Neomycin and Potential Role for ***UGT1A1*28*** Genotype Screening: A Double-Blind, Randomized, Placebo-Controlled Study