Update on the role of nanoliposomal irinotecan in the treatment of metastatic pancreatic cancer

Abstract

Abstract:Median survival for patients with metastatic pancreatic cancer (MPC) treated with combination chemotherapeutic agents such as gemcitabine-based regimens and FOLFIRINOX is currently less than 12 months. This highlights the need for more efficacious first-line, as well as second-line therapies. Nanoliposomal irinotecan, in combination with 5-fluorouracil (5-FU)/folinic acid has recently been assessed as second-line therapy after initial gemcitabine-based therapy. It is the first, second-line treatment approved by the US Food and Drug Administration to treat patients with MPC based on results of the NAnoliPOsomaL Irinotecan (NAPOLI-1) study, which showed that this regimen significantly prolonged progression-free survival (3.1 months versus 1.5 months) and overall survival (6.2 months versus 4.1 months) compared with 5-FU/folinic acid alone. In addition, this study also represented an important step forward in improving the efficacy of previously used chemotherapeutic agents by using nanoformulation to extend pharmacokinetic advantages such as slow clearance, low steady-state volume of distribution, and longer half-life. However, certain adverse effects that are seen more frequently with nanoliposomal irinotecan and 5-FU/folinic acid, compared with 5-FU/folinic acid alone, include neutropenia, fatigue, diarrhea, and nausea/vomiting. This merits close monitoring of patients who are on this combination, since these adverse events may necessitate dose reductions and growth factor support. It is imperative to check UGT1A1 gene status in all patients being considered for treatment with nanoliposomal irinotecan. Patients found to be homozygous for the UGT1A1*28 gene need to be started on a lower initial dose. As we gain more data with clinical use, we anticipate further characterization of the aforementioned toxicities in patients with UGT1A1 gene polymorphisms and other genetic variants.

Computational Estimation of Potential Inhibitors from the Known Drugs against the Main Protease of SARS-CoV-2

“…However, teniposide which is predicted to have a higher affinity to SARS-CoV-2 Mpro has better membrane permeability. Irinotecan is indicated for colorectal and pancreatic cancer treatment or combined with cisplatin for the cure of small cell lung cancer [60][61][62]. The Sn38 moiety is believed to mainly impact the high binding affinity of irinotecan to SARS-CoV-2 Mpro [14].…”

Cancer Chemoprevention Using Nanotechnology-Based Approaches

“…Pancreatic cancer is the third leading cause of all cancer-related deaths in the United States (American Cancer Society, 2019a). Late diagnosis, faster progression, low 5-year survival rate (merely 9%), and high risk of relapse make pancreatic cancer treatment and management challenging despite available firstline drug treatment involving use of gemcitabine combinations and Folfirinox ® (a drug cocktail of fluorouracil, leucovorin, irinotecan, and oxaliplatin) (Rahman et al, 2017;Malatesta et al, 2018;American Cancer Society, 2019a;Desai et al, 2019a;Desai et al, 2019b). Hence, chemoprevention has gained wide attention as an alternative strategy to control the occurrence and relapse.…”

Combination Therapies and Drug Delivery Platforms in Combating Pancreatic Cancer

“…The observed excellent performance of liposomal irinotecan led to initiation of clinical studies evaluating the safety, tolerability, and preliminary efficacy of this nanomedicine in combination with other anticancer therapies (Chen et al, 2015;Wang-Gillam et al, 2016;Glassman et al, 2018). For example, the combination of liposomal irinotecan, 5-FU/folinic acid, and oxaliplatin, which mimics the FOLFORINOX regimen (Rahman et al, 2017), is currently being explored for patients with advanced PDAC who have not received prior chemotherapy or as a preoperative regimen in resectable pancreatic cancer (NCT03528785, NCT02551991, NCT03487016, and NCT03483038). Other liposomal irinotecan plus 5-FU/folinic acid-based therapies under investigation include combinations with BAX2398 (NCT02697058), eryaspase (NCT03665441), cabiralizumab 1 nivolumab (NCT03336216), bermekimab (NCT03207724), and rucaparib (NCT03337087).…”