Liposomal irinotecan (Onivyde): Exemplifying the benefits of nanotherapeutic drugs

Gerard Milano; Federico Innocenti; Hironobu Minami

doi:10.1111/cas.15377

journal article Open Access May 26, 2022

Liposomal irinotecan (Onivyde): Exemplifying the benefits of nanotherapeutic drugs

Gerard Milano

Federico Innocenti Hironobu Minami

Cancer Science Vol. 113 No. 7 pp. 2224-2231 · Wiley

View at Publisher Save 10.1111/cas.15377

Abstract

AbstractIrinotecan is a topoisomerase inhibitor, widely used in treatment of malignancies including pancreatic ductal adenocarcinoma (PDAC) as part of the FOLFIRINOX regimen prescribed as a first‐line treatment in several countries. However, irinotecan has not been successfully introduced as a second‐line treatment for pancreatic cancer and few randomized clinical studies have evaluated its added value. Efficacy of liposomal irinotecan (nal‐IRI) combined with 5‐fluorouracil and leucovorin (5‐FU/LV) was reported in the phase III NAPOLI‐1 trial in metastatic PDAC following failure of gemcitabine‐based therapy. Several features of nal‐IRI pharmacokinetics (PK) could result in better outcomes versus nonliposomal irinotecan. Irinotecan is a prodrug that is converted to active SN‐38 by carboxylesterase enzymes and inactivated by cytochrome P450 3A4/3A5. SN‐38 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‐life and higher area under the concentration‐time curve (0–∞) 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‐IRI 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‐cell lung cancer.

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Details

Published: May 26, 2022
Vol/Issue: 113(7)
Pages: 2224-2231
License: View

Authors

G

Gerard Milano

UPR 7497 Scientific Valorisation Unit Centre Antoine Lacassagne and Côte d’Azur University Nice France

F

Federico Innocenti

Oncology Early Development Abbvie, Inc. San Francisco California USA

H

Hironobu Minami

Medical Oncology and Hematology Kobe University Graduate School of Medicine and Hospital Kobe Japan

Funding

Servier Award: Provided funding for medical writing support

Cite This Article

Gerard Milano, Federico Innocenti, Hironobu Minami (2022). Liposomal irinotecan (Onivyde): Exemplifying the benefits of nanotherapeutic drugs. Cancer Science, 113(7), 2224-2231. https://doi.org/10.1111/cas.15377

Liposomal irinotecan (Onivyde): Exemplifying the benefits of nanotherapeutic drugs

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