Liposomal Irinotecan: A Review in Metastatic Pancreatic Adenocarcinoma

Abstract

Liposomal irinotecan (nal-IRI; Onivyde ® ; also known as pegylated liposomal irinotecan) has been developed with the aim of maximising anti-tumour efficacy while minimising drug-related toxicities compared with the conventional (non-liposomal) formulation of this topoisomerase 1 inhibitor. In combination with 5-fluorouracil and leucovorin (5-FU/LV), nal-IRI is the first agent to be specifically approved for use in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who have progressed following gemcitabine-based therapy. In the pivotal, phase III NAPOLI-1 trial, intravenous administration of nal-IRI + 5-FU/LV to gemcitabine-pretreated patients with mPDAC (as a second-line treatment in approximately two-thirds of cases) was associated with a significant ≈ 2-month median overall survival advantage compared with 5-FU/LV alone. Moreover, adding nal-IRI to 5-FU/LV extended survival with a manageable safety profile and without adversely affecting health-related quality of life, thereby producing significant and clinically meaningful gains in quality-adjusted survival relative to 5-FU/LV alone. Complementing the observed efficacy and safety of nal-IRI in NAPOLI-1 are an increasing number of real-world studies, which provide evidence of the effectiveness of this combination therapy in the treatment of mPDAC that has progressed following gemcitabine-based therapy in contemporary clinical practice in Europe, the USA and East Asia. Thus, nal-IRI, in combination with 5-FU/LV, is the first regimen specifically approved for use as a second- or subsequent-line therapy in gemcitabine-pretreated patients with mPDAC and, as such, represents a valuable treatment option in this setting.

Development and Validation of a Simple-to-Use Nomogram to Predict Early Death in Metastatic Pancreatic Adenocarcinoma

“…The inclusion criteria were as follows (1): the inclusion site codes C25.0–C25.3 and C25.7–C25.9 and (2) histological codes 8140/3, 8225/3, 8480/3, 8481/3, 8500/3, and 8521/3 [according to the International Classification of Tumor Diseases Third Edition (ICD-O-3)]. The cases who were ( 1 ) with a history of previous malignancy ( 2 ), diagnosed by death certificate or autopsy, and ( 3 ) with T0 stage or incomplete information including cause of death, survival months, and race were excluded. Since surgery was not included in the standard treatment guidelines for mPCa, patients lacking specific information on T stage, N stage, or grade were retained in the cohort.…”

“…All over the world, pancreatic adenocarcinoma (PCa) remains one of the most lethal cancers and was reported to be the fourth leading cause of cancer-related deaths in 2020 ( 1 ). On account of its insidious symptoms and high metastatic potential, more than 50% of patients with PCa are diagnosed at an advanced stage, which results in a dismal 5-year relative survival of 6% ( 2 , 3 ).…”

Nano-Based Approved Pharmaceuticals for Cancer Treatment: Present and Future Challenges

“…It exhibits a prolonged plasma half-life and accumulates and persists in high concentration in the bone marrow. Vyxeos TM is indicated as a monotherapy for the treatment of adults with high-risk acute myeloid leukemia [ 92 ].…”

Development of next generation nanomedicine-based approaches for the treatment of cancer: we've barely scratched the surface

“…Additionally, PEGylated liposome formulations also have an increased ability to penetrate the leaky tumour vasculature, thus resulting in enhanced drug accumulation [56][57][58]. More recently, PEGylated formulations such as Onivyde® (PEGylated Irinotecan liposome) for the treatment of advanced pancreatic cancer have been approved, whilst Genexol® (PEG-PLA micelles containing paclitaxel) for the treatment of metastatic breast cancer is currently under clinical investigation [15,53,[59][60][61].…”