title: Development of nanoliposomal irinotecan (nal-IRI, MM-398, PEP02) in the management of metastatic pancreatic cancer.
abstract: BACKGROUND
  Systemic chemotherapy remains the standard of care for patients with advanced pancreatic ductal adenocarcinoma (PDAC). The introductions of FOLFIRINOX and nab-paclitaxel/gemcitabine combinations have improved the first-line treatment outcomes of patients with metastatic PDAC; while second-line therapy options are limited. Based on the results of pivotal NAPOLI-1 study, nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) became the first US Food and Drug Administration (FDA) approved regimen for patients with metastatic PDAC with previous gemcitabine-based chemotherapy in November 2015.
  
  
  METHODS
  We reviewed and summarized the rationale, pharmacokinetics, therapeutic efficacy and adverse events of nal-IRI alone or combined with 5-FU/LV for metastatic PDAC with previous gemcitabine-based chemotherapy.
  
  
  CONCLUSIONS
  In the NAPOLI study, nal-IRI plus 5-FU/LV significantly improved the overall survival, progression-free survival and objective response rate compared to 5-FU/LV alone. The nal-IRI plus 5-FU/LV treatment was associated with a manageable toxicity profile and comparable outcomes in patients with negative demographic characteristics. The relatively sparse of neurotoxicity makes nal-IRI plus 5-FU/LV as a more favorable option than oxaliplatin-containing regimens and the current recommended standard treatment for patients with metastatic PDAC after frontline nab-paclitaxel/gemcitabine treatment. The front-line therapeutic role of nal-IRI is currently under investigation.
authors.affiliation: a Institute of Clinical Medicine, College of Medicine , National Cheng Kung University , Tainan , Taiwan.|b National Institute of Cancer Research , National Health Research Institutes , Tainan , Taiwan.|c Division of Hematology and Oncology, Department of Internal Medicine , National Cheng Kung University Hospital , Tainan , Taiwan.
authors.forename: Nai-Jung
authors.initials: NJ
authors.lastname: Chiang
authors.affiliation: b National Institute of Cancer Research , National Health Research Institutes , Tainan , Taiwan.|c Division of Hematology and Oncology, Department of Internal Medicine , National Cheng Kung University Hospital , Tainan , Taiwan.|d Institute of Clinical Pharmacy and Pharmaceutical Sciences , College of Medicine, National Cheng Kung University , Tainan , Taiwan.
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
authors.affiliation: a Institute of Clinical Medicine, College of Medicine , National Cheng Kung University , Tainan , Taiwan.|e Department of Surgery , National Cheng Kung University Hospital , Tainan , Taiwan.
authors.forename: Yan-Shen
authors.initials: YS
authors.lastname: Shan
authors.affiliation: b National Institute of Cancer Research , National Health Research Institutes , Tainan , Taiwan.|c Division of Hematology and Oncology, Department of Internal Medicine , National Cheng Kung University Hospital , Tainan , Taiwan.|d Institute of Clinical Pharmacy and Pharmaceutical Sciences , College of Medicine, National Cheng Kung University , Tainan , Taiwan.|f Department of Internal Medicine , Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung , Taiwan.
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004338:Drug Combinations; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D013395:Sucrose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D013395:Sucrose; C584112:irinotecan sucrosofate; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Nanoliposomal irinotecan; SN-38; metastatic pancreatic cancer; second-line therapy