Oral probiotic supplementation to alleviate diarrhea induced by fluoropyrimidines or irinotecan-based chemotherapy: A systematic review and meta-analysis
Tippawan Siritientong, Daylia Thet, Nattawut Leelakanok, Nutthada Areepium
Abstract
Fluoropyrimidines and irinotecan cause diarrhea, which can be particularly severe in some cases. Probiotic supplementation is a potential option for managing chemotherapy-induced diarrhea. This study aims to evaluate the efficacy and safety of probiotics in managing diarrhea induced by fluoropyrimidine or irinotecan-based chemotherapy in cancer patients. A literature search was conducted in Cochrane Library, PubMed, ScienceDirect, SciFinder, and Scopus in August 2023. Observational and prospective studies of cancer patients receiving 5-fluorouracil, capecitabine, or irinotecan were included. RevMan (version 5.4.1) was used for statistical analysis. The study protocol was registered in PROSPERO. Of the 9400 records, 24 and 14 studies were included in the systematic review and meta-analysis, respectively. Most studies provided a combination of probiotic strains to patients from the initiation to the completion of chemotherapy cycles. Probiotic supplementation significantly reduced all grade diarrhea (RR = 0.40; 95 % CI: 0.27, 0.60; P < 0.00001, I 2 : 0 %), nausea and vomiting (RR = 0.49; 95 % CI [0.37, 0.67]; P < 0.00001, I 2 : 0 %), bloating (RR = 0.27; 95 % CI [0.11, 0.69]; P = 0.006, I 2 : 0 %) and anorexia (RR = 0.62: 95 % CI [0.43, 0.90]; P = 0.01, I 2 : 39 %) compared to controls. Absolute risk reductions (ARR) ranged from 22.7 % to 28.5 %, with the number needed to treat (NNT) value of 3–5. Moreover, probiotics improved intestinal microbial balance and symptom scales of quality of life. Probiotic supplementation is a promising option to manage chemoradiotherapy-induced diarrhea without serious side effects in cancer patients receiving fluoropyrimidines or irinotecan-based regimens. Given the clinically meaningful ARR and favorable NNT values, probiotics may have a role in clinical practice. However, larger trials are needed to standardize probiotic strain, dosage, duration, and target patient subgroups. PROSPERO database (CRD42023473324) • Probiotics may help manage diarrhea in cancer patients receiving fluoropyrimidine- or irinotecan-based regimens. • This meta-analysis shows that probiotics alleviate all-grade diarrhea, nausea, vomiting, bloating, and anorexia. • This meta-analysis found absolute risk reductions ranging from 22.7% to 28.5%, with a number needed to treat 3 to 5. • Further large, well-controlled trials are needed to define appropriate probiotic strains, dosages, and treatment duration.