title: A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer.
abstract: BACKGROUND
  PEP02, also known as MM-398, is a novel nanoliposomal irinotecan that has improved pharmacokinetics and tumour bio-distribution of the free drug. This phase 2 study evaluated PEP02 monotherapy as second-line treatment for pancreatic cancer.
  
  
  METHODS
  Patients who had metastatic pancreatic adenocarcinoma, Karnofsky performance status ≥70, and had progressed following gemcitabine-based therapy were eligible. Intravenous injection of PEP02 120 mg m(-2) was given every 3 weeks. Simon 2-stage design was used. The primary objective was 3-month survival rate (OS(3-month)).
  
  
  RESULTS
  A total of 40 patients were enrolled. The most common severe adverse events included neutropenia, abdominal pain, asthenia, and diarrhoea. Three patients (7.5%) achieved an objective response, with an additional 17 (42.5%) demonstrating stable disease for a minimum of two cycles. Ten (31.3%) of 32 patients with an elevated baseline CA19-9 had a >50% biomarker decline. The study met its primary end point with an OS(3-month) of 75%, with median progression-free survival and overall survival of 2.4 and 5.2 months, respectively.
  
  
  CONCLUSIONS
  PEP02 demonstrates moderate antitumour activity with a manageable side effect profile for metastatic, gemcitabine-refractory pancreatic cancer patients. Given the limited treatment options available to this patient population, a phase 3 trial of PEP02 (MM-398), referred to as NAPOLI-1, is currently underway.
authors.affiliation: Division of Hematology/Oncology, Comprehensive Cancer Center, University of California, San Francisco, 1600 Divisadero Street, San Francisco, CA 94115, USA. andrewko@medicine.ucsf.edu
authors.forename: A H
authors.initials: AH
authors.lastname: Ko
authors.forename: M A
authors.initials: MA
authors.lastname: Tempero
authors.forename: Y-S
authors.initials: YS
authors.lastname: Shan
authors.forename: W-C
authors.initials: WC
authors.lastname: Su
authors.forename: Y-L
authors.initials: YL
authors.lastname: Lin
authors.forename: E
authors.initials: E
authors.lastname: Dito
authors.forename: A
authors.initials: A
authors.lastname: Ong
authors.forename: Y-W
authors.initials: YW
authors.lastname: Wang
authors.forename: C G
authors.initials: CG
authors.lastname: Yeh
authors.forename: L-T
authors.initials: LT
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016879:Salvage Therapy; D013395:Sucrose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D008081:Liposomes; D013395:Sucrose; D000077146:Irinotecan; C584112:irinotecan sucrosofate; D002166:Camptothecin