Multistrain probiotic may reduce mild, moderate chemotherapy-induced diarrhea

MUNICH — A high-potency multistrain probiotic may help reduce mild or moderate chemotherapy-induced diarrhea among individuals with cancer receiving fluoropyrimidines or irinotecan-based therapy, according to randomized study results presented at European Society for Medical Oncology Congress.

However, the agent likely would have a limited role for reducing incidence of severe cases, researchers said.

“This is probably the first large, randomized, placebo-controlled study to look at the role of [a] multistrain, high-dose probiotic [for] chemotherapy-induced diarrhea,” Atul Sharma, MD, professor of medical oncology at All India Institute of Medical Sciences in New Delhi, India, said in a press release. “Though it did not meet its primary endpoint [of significantly] reducing incidence of grade 3 and 4 diarrhea, it helped to reduce the incidence of all grades of diarrhea. The probiotic also helped [to reduce] levels of inflammatory markers, the significance of which needs to be ascertained.”

Chemotherapy alters the composition of native gut microflora. Chemotherapy-induced diarrhea often is linked to malnutrition and weight loss, and this common side effect often leads patients to take breaks from treatment.

Sharma and colleagues hypothesized that a high-concentration, multistrain probiotic could restore the balance of intestinal flora, thereby decreasing incidence of severe diarrhea.

They conducted a, double-blind, placebo-controlled, single-center study that included 291 patients (mean age, 46 years; 80% men) experiencing chemotherapy-induced diarrhea while receiving fluoropyrimidines or irinotecan-based cancer therapy.

Researchers randomly assigned 145 patients to receive one sachet of multistrain probiotic twice daily. The probiotic — which consisted of 900 billion colony forming units — included four strains of lactobacillus, three strains of bifidobacteria and one strain of streptococcus thermophiles.

The other 146 patients received one sachet of placebo twice daily.

The two groups were balanced with regard to cancer type, body weight and chemotherapy regimen.

Patients started their assigned regimens 14 days before chemotherapy and continued them until 2 weeks after completion of their third chemotherapy cycle.

Incidence of grade 3 or grade 4 diarrhea served as the primary endpoint.

All-grade diarrhea incidence was significantly lower in the treatment group (199 cases vs. 220 cases; P = .019). However, results showed no significant difference in incidence of grade 3 diarrhea (8% vs. 4.1%), grade 4 diarrhea (2% vs. 0%) or rescue medication use (5.5% vs. 6.2%) between the treatment and control groups.

Researchers also assessed inflammatory markers at the conclusion of the study. Results showed patients assigned to the probiotic had lower levels of VEGF (829.5 ± 345 vs. 1,416 ± 379.9; P < .001), calprotectin (485.1 ± 117.2 vs. 617.4 ± 140.1; P < .001) and clusterin (102.4 ± 38 vs. 145.86 ± 31.5; P < .001).

The study if of interest due to the effect of the gut microbiome on response and toxicity among individuals with cancer treated with immune checkpoint inhibitors, as well as trials underway to evaluate fecal transplantation to improve outcomes with checkpoint inhibitor therapy, according to John B.A.G. Haanen, MD, PhD, chief scientific officer for immunotherapy at Netherlands Cancer Institute and professor of translational immunotherapy of cancer at Leiden University in The Netherlands.

“Currently unknown is whether probiotics used in this randomized controlled trial positively or negatively influence the immune system,” Haanen, who was not involved with the study, said in a press release. “With more patients being treated with immunotherapy, before embarking on large-scale usage of probiotics to reduce chemotherapy-induced diarrhea, their effect on the immune system should be investigated.” – Mark Leiser

Reference:

Sharma A, et al. Abstract 1682O_PR. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.

Disclosures: CD Pharma India Pvt. Limited provided funding for this study. The authors report no relevant financial disclosures.