Study protocol on the role of intestinal microbiota in colorectal cancer treatment: a pathway to personalized medicine 2.0

R. Aarnoutse, J. M. P. G. M. de Vos-Geelen, J. Penders, E. G. Boerma, F. A. R. M. Warmerdam, B. Goorts, S. W. M. Olde Damink, Z. Soons, S. S. M. Rensen, M. L. Smidt*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Web of Science)

Abstract

Purpose Investigate in patients with metastatic and/or irresectable colorectal cancer treated with systemic treatment with capecitabine or TAS-102 whether: 1. Intestinal microbiota composition can act as a predictor for response. 2. Intestinal microbiota composition changes during systemic treatment and its relation to chemotoxicity. Background Gut microbiota and host determinants evolve in symbiotic and dependent relationships resulting in a personal ecosystem. In vitro studies showed prolonged and increased response to 5-fluorouracil, a fluoropyrimidine, in the presence of a favorable microbiota composition. Capecitabine and TAS-102 are both fluoropyrimidines used for systemic treatment in colorectal cancer patients. Methods An explorative prospective multicenter cohort study in the Maastricht University Medical Centre+ and Zuyderland Medical Centre will be performed in 66 patients. Before, during, and after three cycles of systemic treatment with capecitabine or TAS-102, fecal samples and questionnaires (concerning compliance and chemotoxicity) will be collected. The response will be measured by CT/ MRI using RECIST-criteria. Fecal microbiota composition will be analyzed with 16S rRNA next-generation sequencing. The absolute bacterial abundance will be assessed with quantitative polymerase chain reaction. Multivariate analysis will be used for statistical analysis. Conclusions We aim to detect a microbiota composition that predicts if patients with metastatic and/ or irresectable colorectal cancer will respond to systemic treatment and/ or experience zero to limited chemotoxicity. If we are able to identify a favorable microbiota composition, fecal microbiota transplantation might be the low-burden alternative to chemotherapy switch in the future.

Original languageEnglish
Pages (from-to)1077-1084
Number of pages8
JournalInternational Journal of Colorectal Disease
Volume32
Issue number7
DOIs
Publication statusPublished - Jul 2017

Keywords

  • Intestinal microbiota
  • Colorectal cancer treatment
  • RANDOMIZED-TRIAL
  • CAPECITABINE
  • CARCINOGENESIS
  • FLUOROURACIL
  • CHEMOTHERAPY

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