Evaluation of the use of probiotics in prevention of irinotecan and /or 5fluorouracil induced diarrhea in patients with Gastrointestinal Cancer

• Grant number: 21/12587-2
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2022
• End date: August 31, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Nora Manoukian Forones
• Grantee: Nora Manoukian Forones
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Gastrointestinal tract tumors (GIT) are in world an important part of cancer cases. In 2020, colorectal cancer was responsible for more than 1.9 million new cases and 935 thousand deaths, representing approximately one in ten of new cases. Fluoropyrimidines and irinotecan are drugs commonly used for treatment of GIT, and diarrhea is one of their main side effect. This is a limiting event that can generate dose reductions and treatment interruptions. The occurrence of diarrhea induced by irinotecan is related to the activity of the patient's intestinal microbiota. Bacterial production of ²-glucuronidases in intestine promotes a transformation of inactive irinotecan´s metabolite (SN38-G) to its active form SN38, causing damage to the bowel wall and, diarrhea onset. Fluoropyrimidines can cause dysbiosis and induce mucositis caused by apoptosis of intestinal cells, in addition to activation inflammatory cytokine expression pathways Recently research suggested that uses of probiotics may contribute to reducing incidence and severity of chemotherapy-induced gastrointestinal toxicity, mainly by reduction of harmful species to intestinal microenvironment and formation of substrates necessary for production of short-chain fatty acids, in particular butyrate, responsible for the maintenance and proper functioning of intestinal mucosa. The objective of this study is evaluating the efficacy of probiotics in preventing irinotecan and/or fluoropyrimidines -induced diarrhea on patients diagnosed with GIT. It is a double-blinded clinical trial among adult and elderly patients diagnosed with primary tumor of the gastrointestinal tract that will start a treatment using irinotecan and/or fluoropyrimidines. Participants will be randomized and allocated into two groups: the control, that will receive magnesium silicate capsules and the intervention which will receive the probiotic 20bi® (Momenta Farma). The follow-up will be for 90 days during which, the participants will have their stool samples evaluated in four distinct moments for the characterization of the intestinal microbiota and answer a questionnaire on their intestinal habits. Participants will be recruited at the Gastro-Oncology outpatient clinic of the Universidade Federal de São Paulo. Expected results include a decrease in the incidence of diarrhea in the group that will use probiotics. (AU)