NalIRI

Nal-IRI, formally nanoliposomal irinotecan, is a liposomal formulation of the chemotherapy agent irinotecan. The liposomal encapsulation is designed to modify pharmacokinetics, prolong circulation, and enhance delivery of irinotecan to tumors. Irinotecan is a prodrug that is converted in the body to SN-38, the active metabolite responsible for antitumor activity.

Nal-IRI is used in the management of metastatic pancreatic ductal adenocarcinoma after progression on gemcitabine. It is approved for use in combination with fluorouracil (5-FU) and leucovorin (LV) as part of a systemic regimen, and is marketed under brand names such as Onivyde in various regions. The therapy is administered intravenously, typically on a predefined schedule every two weeks, in combination with 5-FU/LV as outlined in clinical guidelines.

In clinical trials, nal-IRI plus 5-FU/LV demonstrated an improvement in overall survival compared with 5-FU/LV alone in patients who had previously received gemcitabine. The safety profile includes hematologic and gastrointestinal toxicities, with neutropenia, fatigue, diarrhea, nausea, vomiting, and dehydration among commonly reported adverse effects. As with other chemotherapies, patients require regular monitoring, dose adjustments for toxicity, and supportive care as indicated.

Mechanistically, the liposomal formulation aims to increase intratumoral exposure to SN-38 while reducing peak plasma concentrations, potentially mitigating some systemic toxicities. Nal-IRI represents one approach within liposomal drug-delivery strategies designed to optimize the therapeutic index of irinotecan.

See also: irinotecan, liposomal drug delivery, pancreatic cancer, NAPOLI-1 trial.