Nanoliposomal irinotecan plus fluorouracil and folinic acid as a second-line treatment option in patients with metastatic pancreatic ductal adenocarcinoma: a retrospective cohort study

BMC Cancer. 2021 Nov 3;21(1):1176. doi: 10.1186/s12885-021-08887-1.


Background: According to the NAPOLI-1 trial, nanoliposomal irinotecan (nal-IRI) plus fluorouracil/folinic acid (5-FU/LV) showed improved overall survival compared to fluorouracil alone for patients with metastatic pancreatic cancer who were previously treated with gemcitabine-based therapy. In that trial, Asian patients had frequent dose modification due to haematological toxicity. There has been limited information on the clinical benefits and toxicity of this regimen in real-world settings. In this study, we assessed real-world experience of nal-IRI plus 5-FU/LV in patients with advanced pancreatic cancer after gemcitabine failure.

Methods: We conducted a single institution, retrospective analysis of response, survival and safety in patients who had been treated with nal-IRI with 5-FU/LV. Patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy received nal-IRI (80 mg/m2) with 5-FU/LV every 2 weeks. Kaplan-Meier analysis was performed to obtain median progression free survival and median overall survival. The hazard ratio and 95% confidence interval (CI) were estimated using a stratified Cox regression model. A multivariate Cox proportional hazards regression model was used to identify the effects of clinical factors.

Results: Fifty-one patients received nal-IRI plus 5-FU/LV between January 2015 and December 2020. The median age was 67 years, and males were 58.8%. A total of 40 (78.4%) and 11 (21.6%) patients had received one and two lines of prior chemotherapy before enrollment, respectively. Median progression-free survival was 2.8 months (95% CI 1.8-3.7) and median overall survival was 7.0 months (95% CI 6.0-7.9). Chemotherapy doses were reduced or delayed in 33 (64.7%) patients during the first 6 weeks and median relative dose intensity was 0.87. Thirty-six (70.6%) patients experienced grade 3 or 4 adverse events, most commonly neutropenia (58.8%). Most non-haematologic adverse events were under grade 2. Since the start of first-line chemotherapy, median overall survival was 16.3 months (95% CI 14.1-18.4).

Conclusions: Nal-IRI plus 5-FU/LV seems to be effective, with manageable toxicities, following gemcitabine-based treatment in patients with metastatic pancreatic ductal adenocarcinoma. Nal-IRI plus 5-FU/LV following gemcitabine with nab-paclitaxel is a feasible sequential treatment option in patients with metastatic pancreatic cancer.

Trial registration: Retrospectively registered.

Keywords: Gemcitabine-refractory; Liposomal irinotecan; Pancreatic cancer; Second-line treatment.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Albumins / therapeutic use
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / secondary
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage*
  • Fluorouracil / adverse effects
  • Gemcitabine
  • Humans
  • Irinotecan / administration & dosage*
  • Irinotecan / adverse effects
  • Irinotecan / analogs & derivatives
  • Kaplan-Meier Estimate
  • Leucovorin / administration & dosage*
  • Leucovorin / adverse effects
  • Liposomes
  • Male
  • Middle Aged
  • Nanoconjugates / administration & dosage
  • Nanoconjugates / adverse effects
  • Neutropenia / chemically induced
  • Paclitaxel / therapeutic use
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Progression-Free Survival
  • Proportional Hazards Models
  • Retrospective Studies


  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Antimetabolites, Antineoplastic
  • Liposomes
  • Nanoconjugates
  • Deoxycytidine
  • Irinotecan
  • Paclitaxel
  • Leucovorin
  • Fluorouracil
  • Gemcitabine