Comparison of synbiotics combined with enteral nutrition and prophylactic antibiotics as supportive care in patients with esophageal cancer undergoing neoadjuvant chemotherapy: A multicenter randomized study.

BACKGROUND & AIMS:Established supportive care to reduce the toxicity of neoadjuvant chemotherapy (NAC) is lacking. This multicenter randomized study compared the administration of synbiotics combined with enteral nutrition (EN) versus that of prophylactic antibiotics as supportive care treatment for patients with esophageal cancer undergoing NAC. METHODS:Patients with advanced esophageal cancer scheduled to receive NAC were randomly administered either prophylactic antibiotics (antibiotic group) or synbiotics combined with EN (Syn + EN group). The primary endpoint was the febrile neutropenia (FN) incidence during the first course, and the secondary endpoints were other adverse events, changes in intestinal environment, including fecal microbiota, organic acid concentrations, pH, and chemotherapy tolerability. RESULTS:Eighty-one patients were enrolled. The FN incidence was nonsignificantly lower (P = 0.088) in the Syn + EN group. The incidences of grade 4 neutropenia and grades 2-4 diarrhea were significantly lower in the Syn + EN group (P = 0.014 and 0.033, respectively). Relative dose intensity was significantly higher in the Syn + EN group (92.0 ± 10.9%) than in the antibiotic group (83.2 ± 18.2%) (P = 0.01). Alpfa diversity was significantly higher in the Syn + EN group than in the antibiotic after chemotherapy (P = 0.002). The numbers of Bifidobacterium (P < 0.05), Lacticaseibacillus (P < 0.001), and Enterobacteriaceae (P < 0.001) and the concentration of acetic acid (P < 0.001) were significantly higher in the Syn + EN group than in the antibiotic group after chemotherapy. The severity of diarrhea and occurrence of FN were significantly correlated with Clostridioides difficile abundance and were significantly inversely correlated with acetic acid concentration after chemotherapy. CONCLUSIONS:Synbiotics combined with EN may be an alternative supportive care treatment to prophylactic antibiotics in patients with cancer undergoing toxic chemotherapy (https://jrct.niph.go.jp; jRCTs051180153).