A randomized, double-blind, placebo-controlled trial of probiotics to reduce the severity of oral mucositis induced by chemoradiotherapy for patients with nasopharyngeal carcinoma

Cancer. 2019 Apr 1;125(7):1081-1090. doi: 10.1002/cncr.31907. Epub 2018 Dec 6.

Abstract

Background: The objective of this study was to evaluate the effect of a probiotic combination on the severity of oral mucositis (OM), which is a common, unpreventable complication induced by radiochemotherapy in patients with nasopharyngeal carcinoma who undergo concurrent radiochemotherapy (CCRT).

Methods: Eligible patients (n = 99) with locally advanced nasopharyngeal carcinoma who were undergoing CCRT were randomly assigned (2:1) to receive a probiotic combination or placebo during radiochemotherapy, and the incidence of severe OM (grade 3 or higher) was the primary endpoint.

Results: Patients taking the probiotic combination showed a significant reduction in the severity of OM. The incidences of grade 0, 1, 2, and 3 OM in the placebo group and the probiotic combination group were 0% and 12.07%, 0% and 55.17%, 54.29% and 17.24%, and 45.71% and 15.52%, respectively. Furthermore, CCRT greatly lowered the number of immune cells, whereas the probiotic combination markedly lowered the reduction rates of CD4+ T cells (76.59% vs 52.85%; P < .05), CD8+ T cells (62.94% vs 29.76%; P < .05), and CD3+ T cells (69.72% vs 45.49%; P < .05) in an A-CCRT-P (after treatment with radiotherapy plus chemotherapy plus the probiotic combination) group. High-throughput sequencing results indicated that CCRT had obviously disturbed the intestinal diversity of patients in an A-CCRT (after treatment with radiotherapy plus chemotherapy plus a placebo) group, whereas the probiotic combination distinctly restored the microbial diversity in the A-CCRT-P group toward that of healthy people and a B-CCRT-P (before the treatment of radiotherapy plus chemotherapy plus the probiotic combination) group.

Conclusions: A probiotic combination significantly enhances the immune response of patients and reduces the severity of OM through modification of gut microbiota.

Keywords: concurrent radiochemotherapy; microbial diversity; nasopharyngeal carcinoma; oral mucositis; probiotics.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / adverse effects
  • Bifidobacterium longum
  • Chemoradiotherapy / adverse effects*
  • Cisplatin / adverse effects
  • DNA, Bacterial / analysis
  • Double-Blind Method
  • Enterococcus faecium
  • Female
  • Gastrointestinal Microbiome* / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lactobacillus
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma / therapy*
  • Nasopharyngeal Neoplasms / therapy*
  • Probiotics / therapeutic use*
  • Radiotherapy, Intensity-Modulated / adverse effects
  • Sequence Analysis, DNA
  • Severity of Illness Index
  • Stomatitis / prevention & control*

Substances

  • Antineoplastic Agents
  • DNA, Bacterial
  • Cisplatin

Supplementary concepts

  • Lactobacillus delbrueckii subsp. lactis