Management of diarrhea in patients receiving liposomal irinotecan-based regimens: a narrative review of mechanisms, clinical impact, and evidence-based strategies.
- 1Department of Clinical Oncology, Fondazione Poliambulanza, Brescia, Italy.
Abstract
Liposomal irinotecan (nal-IRI) in combination with 5-fluorouracil and leucovorin (5-FU/LV) represents the standard second-line treatment for metastatic pancreatic ductal adenocarcinoma (mPDAC) following progression on gemcitabine-based therapy. Despite its demonstrated survival benefit, diarrhea remains a clinically significant toxicity that can compromise dose intensity, treatment adherence, and quality of life. This review provides a comprehensive and updated overview of the pathophysiology, incidence, and evidence-based management of diarrhea associated with nal-IRI-based regimens. A structured narrative review of the available literature was performed, including prospective randomized trials, supportive care guidelines, pharmacogenomic data, and emerging translational evidence. Given the heterogeneity of study designs and the limited number of nal-IRI-specific supportive care trials, a formal meta-analysis was not feasible. Diarrhea associated with nal-IRI is mechanistically complex, encompassing acute cholinergic and delayed secretory components mediated by SN-38-induced mucosal injury and enterohepatic recirculation. Grade 3-4 diarrhea occurs in approximately 13-20% of patients across major pancreatic cancer trials. Evidence-based management strategies are presented, including pharmacologic interventions (atropine, loperamide, octreotide, fluoroquinolones), supportive care, and dose modification protocols. Emerging approaches-including gut microbiome modulation, beta-glucuronidase inhibitors, and novel antisecretory agents-are also reviewed. A multidisciplinary, proactive management approach-beginning before the first nal-IRI dose-is essential to minimize diarrhea-related morbidity and optimize treatment outcomes. Integration of pharmacogenomic data and emerging biomarkers-particularly UGT1A1*28 genotyping and gut microbiome β-glucuronidase activity profiling-may further individualize risk stratification and management in this patient population.
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BibTeX
@article{zaniboni2026management,
title = {{Management of diarrhea in patients receiving liposomal irinotecan-based regimens: a narrative review of mechanisms, clinical impact, and evidence-based strategies.}},
author = {Alberto Zaniboni},
journal = {Journal of gastrointestinal oncology},
year = {2026},
month = sep,
doi = {10.21037/jgo-2026-0627},
url = {https://europepmc.org/article/MED/42996839},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Management of diarrhea in patients receiving liposomal irinotecan-based regimens: a narrative review of mechanisms, clinical impact, and evidence-based strategies.
AU - Alberto Zaniboni
PY - 2026
DA - 2026/09/14
JO - Journal of gastrointestinal oncology
DO - 10.21037/jgo-2026-0627
UR - https://europepmc.org/article/MED/42996839
AB - Liposomal irinotecan (nal-IRI) in combination with 5-fluorouracil and leucovorin (5-FU/LV) represents the standard second-line treatment for metastatic pancreatic ductal adenocarcinoma (mPDAC) following progression on gemcitabine-based therapy. Despite its demonstrated survival benefit, diarrhea remains a clinically significant toxicity that can compromise dose intensity, treatment adherence, and quality of life. This review provides a comprehensive and updated overview of the pathophysiology, incidence, and evidence-based management of diarrhea associated with nal-IRI-based regimens. A structured narrative review of the available literature was performed, including prospective randomized trials, supportive care guidelines, pharmacogenomic data, and emerging translational evidence. Given the heterogeneity of study designs and the limited number of nal-IRI-specific supportive care trials, a formal meta-analysis was not feasible. Diarrhea associated with nal-IRI is mechanistically complex, encompassing acute cholinergic and delayed secretory components mediated by SN-38-induced mucosal injury and enterohepatic recirculation. Grade 3-4 diarrhea occurs in approximately 13-20% of patients across major pancreatic cancer trials. Evidence-based management strategies are presented, including pharmacologic interventions (atropine, loperamide, octreotide, fluoroquinolones), supportive care, and dose modification protocols. Emerging approaches-including gut microbiome modulation, beta-glucuronidase inhibitors, and novel antisecretory agents-are also reviewed. A multidisciplinary, proactive management approach-beginning before the first nal-IRI dose-is essential to minimize diarrhea-related morbidity and optimize treatment outcomes. Integration of pharmacogenomic data and emerging biomarkers-particularly UGT1A1*28 genotyping and gut microbiome β-glucuronidase activity profiling-may further individualize risk stratification and management in this patient population.
SN - 2078-6891
SN - 2219-679X
ER -