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Review
. 2017 Jul;10(7):563-572.
doi: 10.1177/1756283X17705328. Epub 2017 Apr 26.

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

Fnu Asad Ur Rahman  1 , Saeed Ali  1 , Muhammad Wasif Saif  2
Affiliations
Review

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

Fnu Asad Ur Rahman et al. Therap Adv Gastroenterol. 2017 Jul.

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.

Keywords: gemcitabine; irinotecan liposome injection; nanoliposomal irinotecan; pancreatic cancer.

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Conflict of interest statement

Conflict of interest statement: MWS has received a grant from Merrimack Pharmaceuticals for research funding. In addition, he has been selected for the Speaker bureau. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.
Schema of the NAPOLI-1 study. FU, fluorouracil; KPS, Karnofsky performance status; LV, leucovorin.
Figure 2.
Figure 2.
Median survival in the NAPOLI-1 study. CI, confidence interval; 5-FU, 5-fluorouracil; HR, hazard ratio; LV, leucovorin; OS, overall survival.
See this image and copyright information in PMC

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