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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2016

01-11-2016 | Review Article

Irinotecan- and 5-fluorouracil-induced intestinal mucositis: insights into pathogenesis and therapeutic perspectives

Authors: Ronaldo A. Ribeiro, Carlos W. S. Wanderley, Deysi V. T. Wong, José Maurício S. C. Mota, Caio A. V. G. Leite, Marcellus H. L. P. Souza, Fernando Q. Cunha, Roberto C. P. Lima-Júnior

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2016

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Abstract

Purpose

Intestinal mucositis and diarrhea are common manifestations of anticancer regimens that include irinotecan, 5-fluorouracil (5-FU), and other cytotoxic drugs. These side effects negatively impact therapeutic outcomes and delay subsequent cycles of chemotherapy, resulting in dose reductions and treatment discontinuation. Here, we aimed to review the experimental evidence regarding possible new targets for the management of irinotecan- and 5-FU-related intestinal mucositis.

Methods

A literature search was performed using the PubMed and MEDLINE databases. No publication time limit was set for article inclusion.

Results

Here, we found that clinical management of intestinal mucositis and diarrhea is somewhat ineffective at reducing symptoms, possibly due to a lack of specific targets for modulation. We observed that IL-1β contributes to the apoptosis of enterocytes in mucositis induced by 5-FU. However, 5-FU-related mucositis is far less thoroughly investigated with regard to specific molecular targets when compared to irinotecan-related disease. Several studies have proposed that a correlation exists between the intestinal microbiota, the enterohepatic recirculation of active metabolites of irinotecan, and the establishment of mucositis. However, as reviewed here, this association seems to be controversial. In addition, the pathogenesis of irinotecan-induced mucositis appears to be orchestrated by interleukin-1/Toll-like receptor family members, leading to epithelial cell apoptosis.

Conclusions

IL-1β, IL-18, and IL-33 and the receptors IL-1R, IL-18R, ST2, and TLR-2 are potential therapeutic targets that can be modulated to minimize anticancer agent-associated toxicity, optimize cancer treatment dosing, and improve clinical outcomes. In this context, the pathogenesis of mucositis caused by other anticancer agents should be further investigated.
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Metadata
Title
Irinotecan- and 5-fluorouracil-induced intestinal mucositis: insights into pathogenesis and therapeutic perspectives
Authors
Ronaldo A. Ribeiro
Carlos W. S. Wanderley
Deysi V. T. Wong
José Maurício S. C. Mota
Caio A. V. G. Leite
Marcellus H. L. P. Souza
Fernando Q. Cunha
Roberto C. P. Lima-Júnior
Publication date
01-11-2016
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2016
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-016-3139-y

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