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

被引：27
作者：
Aarnoutse, R. [1 ,2 ]
de Vos-Geelen, J. M. P. G. M. [3 ]
Penders, J. [4 ]
Boerma, E. G. [5 ]
Warmerdam, F. A. R. M. [6 ]
Goorts, B. [1 ,2 ]
Damink, S. W. M. Olde [2 ,7 ]
Soons, Z. [7 ]
Rensen, S. S. M. [7 ]
Smidt, M. L. [1 ,2 ]
机构：
[1] Maastricht Univ, Med Ctr, GROW Sch Oncol & Dev Biol, Univ Singel 40, NL-6229 ER Maastricht, Netherlands
[2] Maastricht Univ, Med Ctr, Dept Surg, P Debyelaan 25, NL-6229 HX Maastricht, Netherlands
[3] Maastricht Univ, Med Ctr, Dept Med Oncol, P Debyelaan 25, NL-6229 HX Maastricht, Netherlands
[4] Maastricht Univ, Med Ctr, Dept Med Microbiol, P Debyelaan 25, NL-6229 HX Maastricht, Netherlands
[5] Zuyderland Med Ctr, Dept Surg, Dr H van der Hoffpl 1, NL-6162 BG Geleen, Netherlands
[6] Zuyderland Med Ctr, Dept Med Oncol, Dr H van der Hoffpl 1, NL-6162 BG Geleen, Netherlands
[7] Maastricht Univ, Med Ctr, NUTRIM Sch Nutr & Translat Res Metab, Univ Singel 40, NL-6229 ER Maastricht, Netherlands
来源：
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE | 2017年 / 32卷 / 07期
关键词：
Intestinal microbiota; Colorectal cancer treatment; RANDOMIZED-TRIAL; CARCINOGENESIS; FLUOROURACIL; CAPECITABINE;
D O I：
10.1007/s00384-017-2819-3
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
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.
引用
收藏
页码：1077 / 1084
页数：8
相关论文
共 26 条
[1]   Combination Therapy of Lactobacillus plantarum Supernatant and 5-Fluouracil Increases Chemosensitivity in Colorectal Cancer Cells [J].
An, JaeJin ;
Ha, Eun-Mi .
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY, 2016, 26 (08) :1490-1503
[2]   Pharmacometabonomic Profiling as a Predictor of Toxicity in Patients with Inoperable Colorectal Cancer Treated with Capecitabine [J].
Backshall, Alexandra ;
Sharma, Rohini ;
Clarke, Stephen J. ;
Keun, Hector C. .
CLINICAL CANCER RESEARCH, 2011, 17 (09) :3019-3028
[3]  
Borges-Canha M, 2015, REV ESP ENFERM DIG, V107, P659, DOI 10.17235/reed.2015.3830/2015
[4]   QIIME allows analysis of high-throughput community sequencing data [J].
Caporaso, J. Gregory ;
Kuczynski, Justin ;
Stombaugh, Jesse ;
Bittinger, Kyle ;
Bushman, Frederic D. ;
Costello, Elizabeth K. ;
Fierer, Noah ;
Pena, Antonio Gonzalez ;
Goodrich, Julia K. ;
Gordon, Jeffrey I. ;
Huttley, Gavin A. ;
Kelley, Scott T. ;
Knights, Dan ;
Koenig, Jeremy E. ;
Ley, Ruth E. ;
Lozupone, Catherine A. ;
McDonald, Daniel ;
Muegge, Brian D. ;
Pirrung, Meg ;
Reeder, Jens ;
Sevinsky, Joel R. ;
Tumbaugh, Peter J. ;
Walters, William A. ;
Widmann, Jeremy ;
Yatsunenko, Tanya ;
Zaneveld, Jesse ;
Knight, Rob .
NATURE METHODS, 2010, 7 (05) :335-336
[5]   Random forests for genomic data analysis [J].
Chen, Xi ;
Ishwaran, Hemant .
GENOMICS, 2012, 99 (06) :323-329
[6]   Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB [J].
DeSantis, T. Z. ;
Hugenholtz, P. ;
Larsen, N. ;
Rojas, M. ;
Brodie, E. L. ;
Keller, K. ;
Huber, T. ;
Dalevi, D. ;
Hu, P. ;
Andersen, G. L. .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2006, 72 (07) :5069-5072
[7]   Gastric microbiota and carcinogenesis: the role of non-Helicobacter pylori bacteria - A systematic review [J].
Dias-Jacome, Emanuel ;
Libanio, Diogo ;
Borges-Canha, Marta ;
Galaghar, Ana ;
Pimentel-Nunes, Pedro .
REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS, 2016, 108 (09) :530-540
[8]   New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].
Eisenhauer, E. A. ;
Therasse, P. ;
Bogaerts, J. ;
Schwartz, L. H. ;
Sargent, D. ;
Ford, R. ;
Dancey, J. ;
Arbuck, S. ;
Gwyther, S. ;
Mooney, M. ;
Rubinstein, L. ;
Shankar, L. ;
Dodd, L. ;
Kaplan, R. ;
Lacombe, D. ;
Verweij, J. .
EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247
[9]   DPD and UGT1A1 deficiency in colorectal cancer patients receiving triplet chemotherapy with fluoropyrimidines, oxaliplatin and irinotecan [J].
Falvella, Felicia Stefania ;
Cheli, Stefania ;
Martinetti, Antonia ;
Mazzali, Cristina ;
Iacovelli, Roberto ;
Maggi, Claudia ;
Gariboldi, Manuela ;
Pierotti, Marco Alessandro ;
Di Bartolomeo, Maria ;
Sottotetti, Elisa ;
Mennitto, Roberta ;
Bossi, Ilaria ;
de Braud, Filippo ;
Clementi, Emilio ;
Pietrantonio, Filippo .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2015, 80 (03) :581-588
[10]   Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer [J].
Giacchetti, S ;
Perpoint, B ;
Zidani, R ;
Le Bail, N ;
Faggiuolo, R ;
Focan, C ;
Chollet, P ;
Llory, JF ;
Letourneau, Y ;
Coudert, B ;
Bertheaut-Cvitkovic, F ;
Larregain-Fournier, D ;
Le Rol, A ;
Walter, S ;
Adam, R ;
Misset, JL ;
Lévi, F .
JOURNAL OF CLINICAL ONCOLOGY, 2000, 18 (01) :136-147
123