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However, irinotecan has not been successfully introduced as a second\u2010line treatment for pancreatic cancer and few randomized clinical studies have evaluated its added value. Efficacy of liposomal irinotecan (nal\u2010IRI) combined with 5\u2010fluorouracil and leucovorin (5\u2010FU\/LV) was reported in the phase III NAPOLI\u20101 trial in metastatic PDAC following failure of gemcitabine\u2010based therapy. Several features of nal\u2010IRI pharmacokinetics (PK) could result in better outcomes versus nonliposomal irinotecan. Irinotecan is a prodrug that is converted to active SN\u201038 by carboxylesterase enzymes and inactivated by cytochrome P450 3A4\/3A5. SN\u201038 is inactivated by UGT1A1 enzymes. Individual variations in their expression and activity could influence enhanced localized irinotecan activity and toxicity. Liposomal irinotecan exploits the enhanced permeability and retention effect in cancer, accumulating in tumor tissues. Liposomal irinotecan also has a longer half\u2010life and higher area under the concentration\u2010time curve (0\u2013\u221e) than nonliposomal irinotecan, as the liposomal formulation protects cargo from premature metabolism in the plasma. This results in irinotecan activation in tumor tissue, leading to enhanced cytotoxicity. Importantly, despite the longer exposure, overall toxicity for nal\u2010IRI is no worse than nonliposomal irinotecan. Liposomal irinotecan exemplifies how liposomal encapsulation of a chemotherapeutic agent can alter its PK properties, improving clinical outcomes for patients. Liposomal irinotecan is currently under investigation in other malignancies including biliary tract cancer (amongst other gastrointestinal cancers), brain tumors, and small\u2010cell lung cancer.<\/jats:p>","DOI":"10.1111\/cas.15377","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T07:13:14Z","timestamp":1650525194000},"page":"2224-2231","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":187,"title":["Liposomal irinotecan (Onivyde): Exemplifying the benefits of nanotherapeutic drugs"],"prefix":"10.1111","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2478-0040","authenticated-orcid":false,"given":"G\u00e9rard","family":"Milano","sequence":"first","affiliation":[{"name":"UPR 7497 Scientific Valorisation Unit Centre Antoine Lacassagne and C\u00f4te d\u2019Azur University  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Innocenti","sequence":"additional","affiliation":[{"name":"Oncology Early Development Abbvie, Inc.  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