Nanomedicine developments in the treatment of metastatic pancreatic cancer: focus on nanoliposomal irinotecan

Abstract

Nanoliposomal irinotecan (nal-IRI) was originally developed using an efficient and high-loading capacity system to encapsulate irinotecan within a liposomal carrier, producing a therapeutic agent with improved biodistribution and pharmacokinetic characteristics compared to free drug. Specifically, administration of nal-IRI results in prolonged exposure of SN-38, the active metabolite of irinotecan, within tumors, while at the same time offering the advantage of less systemic toxicity than traditional irinotecan. These favorable properties of nal-IRI, confirmed in a variety of tumor xenograft models, led to its clinical evaluation in a number of disease indications for which camptothecins have proven activity, including in colorectal, gastric, and pancreatic cancers. The culmination of these clinical trials was the NAPOLI-1 (Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy) trial, an international Phase III study evaluating nal-IRI both alone and in combination with 5-fluorouracil and leucovorin in patients with metastatic pancreatic adenocarcinoma following progression on gemcitabine-based chemotherapy. Positive results from NAPOLI-1 led to approval of nal-IRI (with 5-fluorouracil/leucovorin) in October 2015 by the US Food and Drug Administration specifically for the treatment of metastatic pancreatic cancer in the second-line setting and beyond, a clinical context in which there had previously been no accepted standard of care. As such, nal-IRI represents an important landmark in cancer drug development, and potentially ushers in a new era where a greater number of patients with advanced pancreatic cancer can be sequenced through multiple lines of therapy translating into meaningful improvements in survival.

Liposomal Irinotecan: A Review in Metastatic Pancreatic Adenocarcinoma

“…Liposomal irinotecan (nal-IRI; Onivyde ® ) (also known as pegylated liposomal irinotecan and abbreviated as MM-398 or PEP02) is an intravenously-administered, liposomal-encapsulated formulation of irinotecan that has been developed to overcome the pharmacological and clinical limitations of the conventional (non-liposomal) formulation of the drug, with the overall aim of maximising anti-tumour efficacy while minimising drug-related toxicities [ 8 , 12 , 13 , 16 ]. Liposomal irinotecan, in combination with 5-FU and LV, has been approved in several regions or countries worldwide, including the EU [ 17 ], the USA [ 18 ], Canada [ 19 ], Australia [ 20 ], Japan [ 21 ], South Korea [ 22 ] and Taiwan [ 22 ], for the treatment of mPDAC in patients who have progressed following gemcitabine-based therapy.…”

Dual Inhibition of IGF-1R and ErbB3 Enhances the Activity of Gemcitabine and Nab-Paclitaxel in Preclinical Models of Pancreatic Cancer

“…Despite the largest increase in survival for FOLFIRINOX, this regimen is characterized by substantial toxicity and is usually restricted to patients with good performance status. Recently, nanoliposomal irinotecan (Onivyde), in combination with fluorouracil and leucovorin, was approved by the US Food and Drug Administration for the treatment of patients with metastatic disease who previously received gemcitabine-based therapy (5,6). Although this combination extends survival and has a manageable safety profile, mOS is 6.1 months (6).…”

Pancreatic Cancer, Current Therapeutic Approaches and Possible Prospects

“…Данный факт очень важен, поскольку nal-IRI -это первый агент, специально одобренный для использования при лечении 2-й линии метастатического РПЖ. мОВ в группе пациентов, получавших иринотекан c 5-ФУ / лейковорином в качестве терапии 2-й линии, составила 6,1 мес, тогда как в группе больных, получавших лечение только 5-ФУ / лейковорином -4,2 мес [2,24].…”