Prevention of irinotecan-induced diarrhoea by oral carbonaceous adsorbent (Kremezin™) in cancer patients

Maeda, Yorinobu; Ohune, Terumasa; Nakamura, Mamoru; Yamasaki, Miho; Kiribayashi, Yoshie; Murakami, Teruo

doi:10.3892/or.12.3.581

Cited by 9 publications

(8 citation statements)

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“…In Kremezin treated rats the frequency of diarrhea was reduced by approximately 50% as compared to non treated rats along with a decrease in severity [162]. In a clinical trial 2 gram Kremezin three times a day, during and after CPT-11 treatment decreased CID along with a small effect on pharmacokinetics of CPT-11 and its metabolites [163]. …”

Section: Strategies To Block Delayed Diarrheamentioning

confidence: 99%

Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis

Swami

Goel

Mani

2013

CDT

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CPT-11 (irinotecan), a DNA topoisomerase I inhibitor is one of the main treatments for colorectal cancer. The main dose limiting toxicities are neutropenia and late onset diarrhea. Though neutropenia is manageable, CPT-11 induced diarrhea is frequently severe, resulting in hospitalizations, dose reductions or omissions leading to ineffective treatment administration. Many potential agents have been tested in preclinical and clinical studies to prevent or ameliorate CPT-11 induced late onset diarrhea. It is predicted that prophylaxis of CPT-11 induced diarrhea will reduce sub-therapeutic dosing as well as hospitalizations and will eventually lead to dose escalations resulting in better response rates. This article reviews various experimental agents and strategies employed to prevent this debilitating toxicity. Covered topics include schedule/dose modification, intestinal alkalization, structural/chemical modification, genetic testing, anti-diarrheal therapies, transporter (ABCB1, ABCC2, BCRP2) inhibitors, enzyme (β-glucuronidase, UGT1A1, CYP3A4, carboxylesterase, COX-2) inducers and inhibitors, probiotics, antibiotics, adsorbing agents, cytokine and growth factor activators and inhibitors and other miscellaneous agents.

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Section: Strategies To Block Delayed Diarrheamentioning

confidence: 99%

Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis

Swami

Goel

Mani

2013

CDT

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“…and Maeda et al . demonstrated the efficacy of oral alkalization and oral activated charcoal in preventing the intestinal re‐absorption of SN‐38 and/or CPT‐11, respectively . Treatment with probenecid, an MRP2 inhibitor, is also reported to reduce the intestinal toxicity by decreasing the MRP2‐mediated biliary excretion of CPT‐11, SN‐38 and SN‐38G, without any significant effects on myelosuppression…”

Section: Introductionmentioning

confidence: 99%

Effect of genistein, a natural soy isoflavone, on the pharmacokinetics and intestinal toxicity of irinotecan hydrochloride in rats

Yokooji

Kawabe

Mori

et al. 2012

Journal of Pharmacy and Pharmacology

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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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Prevention of irinotecan-induced diarrhoea by oral carbonaceous adsorbent (Kremezin™) in cancer patients

Cited by 9 publications

References 0 publications

Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis

Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis

Effect of genistein, a natural soy isoflavone, on the pharmacokinetics and intestinal toxicity of irinotecan hydrochloride in rats

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

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Prevention of irinotecan-induced diarrhoea by oral carbonaceous adsorbent (Kremezin™) in cancer patients

Cited by 9 publications

References 0 publications

Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis

Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis

Effect of genistein, a natural soy isoflavone, on the pharmacokinetics and intestinal toxicity of irinotecan hydrochloride in rats

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

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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