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

Ribeiro, Ronaldo A., Wanderley, Carlos W. S., Wong, Deysi V. T., Mota, José Maurício S. C., Leite, Caio A. V. G., Souza, Marcellus H. L. P., Cunha, Fernando Q., Lima-Júnior, Roberto C. P.·2016·Cancer Chemotherapy and Pharmacology
DOI 10.1007/s00280-016-3139-y
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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…

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Metadata

Authors
Ribeiro, R. A., Wanderley, C. W. S., Wong, D. V. T., Mota, J. M. S. C., Leite, C. A. V. G., Souza, M. H. L. P., Cunha, F. Q., & Lima-Júnior, R. C. P.
Venue
Cancer Chemotherapy and Pharmacology
Publisher
Springer Science and Business Media LLC
Published
2016-09-02
Volume
78
Issue
5
Pages
881-893
ISSN
  • 0344-5704
  • 1432-0843
DOI
10.1007/s00280-016-3139-y
Cited by
146
References
4
Language
en
Licence
www.springer.com/tdm (unspecified)
Funders
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-PROEX 2862/2013)
  • Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (PR2-0101-00054.01.00/15)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (307143/2014-7, 458872/2014-8)

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