Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer : A Randomized, Double-blind, Placebo-Controlled, Phase II Study

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de Clercq , N C , van den Ende , T , Prodan , A , Hemke , R , Davids , M , Pedersen , H K , Nielsen , H B , Groen , A K , de Vos , W M , van Laarhoven , H W M & Nieuwdorp , M 2021 , ' Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer : A Randomized, Double-blind, Placebo-Controlled, Phase II Study ' , Clinical Cancer Research , vol. 27 , no. 13 , pp. 3784-3792 . https://doi.org/10.1158/1078-0432.CCR-20-4918

Title: Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer : A Randomized, Double-blind, Placebo-Controlled, Phase II Study
Author: de Clercq, Nicolien C.; van den Ende, Tom; Prodan, Andrei; Hemke, Robert; Davids, Mark; Pedersen, Helle K.; Nielsen, Henrik B.; Groen, A. K.; de Vos, Willem M.; van Laarhoven, Hanneke W. M.; Nieuwdorp, Max
Contributor organization: Department of Bacteriology and Immunology
Willem Meindert Vos de / Principal Investigator
de Vos & Salonen group
Date: 2021-07
Language: eng
Number of pages: 9
Belongs to series: Clinical Cancer Research
ISSN: 1078-0432
DOI: https://doi.org/10.1158/1078-0432.CCR-20-4918
URI: http://hdl.handle.net/10138/346527
Abstract: Purpose Cachexia is a multifactorial syndrome, associated with poor survival in patients with cancer, and is influenced by the gut microbiota. We investigated the effects of fecal microbiota transplantation (FMT) on cachexia and treatment response in patients with advanced gastroesophageal cancer. Experimental Design: In a double-blind randomized placebo-controlled trial performed in the Amsterdam University Medical Center, we assigned 24 cachectic patients with metastatic HER2-negative gastroesophageal cancer to either allogenic FMT (healthy obese donor) or autologous FMT, prior to palliative chemotherapy (capecitabine and oxaliplatin). Primary objective was to assess the effect of allogenic FMT on satiety. Secondary outcomes were other features of cachexia, along with disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity. Finally, exploratory analyses were performed on the effect of FMT on gut microbiota composition (metagenomic sequencing) and metabolites (untargeted metabolomics). Results: Allogenic FMT did not improve any of the cachexia outcomes. Patients in the allogenic group (n = 12) had a higher DCR at 12 weeks (P = 0.035) compared with the autologous group (n = 12), longer median OS of 365 versus 227 days [ HR = 0.38; 95% confidence interval (CI), 0.14-1.05; P = 0.057] and PFS of 204 versus 93 days (HR = 0.50; 95% CI, 0.21-1.20; P = 0.092). Patients in the allogenic group showed a significant shift in fecal microbiota composition after FMT (P = 0.010) indicating proper engraftment of the donor microbiota. Conclusions: FMT from a healthy obese donor prior to first-line chemotherapy did not affect cachexia, but may have improved response and survival in patients with metastatic gastroesophageal cancer. These results provide a rational for larger FMT trials.
Subject: GUT MICROBIOTA
WEIGHT-LOSS
CACHEXIA
CHEMOTHERAPY
CAPECITABINE
OXALIPLATIN
TOXICITY
3122 Cancers
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: acceptedVersion


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