Distinct safety profiles of liposomal and conventional irinotecan: insights from clinical experience and real-world data

Background: Liposomal irinotecan (nal-IRI) and conventional irinotecan (IRI) represent two formulations with distinct pharmacokinetic properties, yet their comparative safety profiles remain incompletely characterized. This study aimed to systematically evaluate their adverse event (AE) patterns through integrated pharmacovigilance and clinical analyses. Methods: We conducted a dual-approach investigation combining: (1) a single-center retrospective study of 308 pancreatic cancer patients (nal-IRI = 131; IRI = 177) treated between December 2023-September 2024, and (2) disproportionality analysis of FAERS database reports (2004-2024) using reporting odds ratios (RORs) and proportional reporting ratios (PRRs). Results: The retrospective study demonstrated significantly higher incidence of grade 3-4 leukopenia with nal-IRI (9.16% vs. 3.39%, p < 0.05) and earlier onset of hematologic/hepatic toxicities (median time difference: 20-30 days, p < 0.05). No significant differences were observed in non-hematologic toxicities between groups. FAERS analysis revealed distinct AE patterns: nal-IRI reports were predominantly associated with fatal outcomes (43.76%) and cholangitis (PRR = 996.70) in pancreatic cancer patients, while IRI showed conventional chemotherapy toxicities in colorectal cancer patients. Conclusion: These findings suggest that nal-IRI and IRI exhibit distinct safety profiles, which are partly attributable to differences in their liposomal pharmacokinetics, but also reflect the underlying disease characteristics and prognostic profiles of their respective patient populations. These findings emphasize the need for enhanced monitoring during initial nal-IRI treatment cycles and suggest differential safety management strategies for the two formulations. Future multicenter studies with pharmacokinetic assessments are warranted to further elucidate these differences.