title: A Phase 2 Randomized, Double-Blind, Multicenter Trial of Imexon Plus Gemcitabine Versus Gemcitabine Plus Placebo in Patients With Metastatic Chemotherapy-naïve Pancreatic Adenocarcinoma.
abstract: Imexon is a cyanoaziridine-derived iminopyrrolidone which has synergistic cytotoxicity with gemcitabine. A phase 1 study of the combination demonstrated good tolerance with encouraging clinical activity and thus we conducted this randomized phase II study.
  
  
  
  Patients with measurable, metastatic, treatment-naive pancreatic adenocarcinoma were randomized 1:1 to receive gemcitabine at 1000 mg/m days 1, 8, and 15 with either imexon, 875 mg/m or placebo days 1, 8, and 15 every 28 days. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and response rate.
  
  
  
  A total of 142 patients were randomized, 72 to the imexon containing arm and 70 to the placebo arm. Patients in the imexon arm received an average of 3.6 cycles (range, 1 to 23) compared with 4.4 (range, 1 to 21) in the placebo arm. There was no increased rate of ≥grade 3 toxicity in the imexon arm. Seven patients had objective responses in the imexon arm (13.7%), whereas 9 did in the placebo arm (17%). In the imexon arm, 23 patients had ≥50% reduction in CA 19-9 from baseline (33%), whereas 22 did in the placebo arm (31.4%). The median progression-free survival was 2.8 months in the imexon arm (95% confidence interval [CI], 2.0-4.1 m) and 3.8 months in the placebo arm (95% CI, 2.2-4.7 m), P=0.504. The median overall survival time in the imexon arm was 5.2 months (95% CI, 4.2-6.7 m) as compared with 6.8 m (95% CI, 4.9-8.5 m) in the placebo arm, P=0.6822.
  
  
  
  The combination of imexon and gemcitabine does not result in improved outcome as initial therapy of metastatic pancreatic adenocarcinoma.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Cohen
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Zalupski
authors.affiliation: US Oncology (Virginia Oncology Associates), Norfolk, VA.
authors.forename: Paul
authors.initials: P
authors.lastname: Conkling
authors.affiliation: Lahey Clinic, Burlington, MA.
authors.forename: Francis
authors.initials: F
authors.lastname: Nugent
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Wen Wee
authors.initials: WW
authors.lastname: Ma
authors.affiliation: Arizona Clinical Research Center.
authors.forename: Manuel
authors.initials: M
authors.lastname: Modiano
authors.affiliation: Northern Indiana Cancer Research Consortium, South Bend, IN.
authors.forename: Rolan
authors.initials: R
authors.lastname: Pascual
authors.affiliation: University of New Mexico, Albuquerque, NM.
authors.forename: Fa Chyi
authors.initials: FC
authors.lastname: Lee
authors.affiliation: Scott and White Hospital and Clinics, Temple, TX.
authors.forename: Lucas
authors.initials: L
authors.lastname: Wong
authors.affiliation: Amplimed Corporation, Tuscon, AZ.
authors.forename: Evan
authors.initials: E
authors.lastname: Hersh
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D005260:Female; D006588:Hexanones / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000077982:Progression-Free Survival; D000093542:Gemcitabine
chemical_list: D006588:Hexanones; D003841:Deoxycytidine; C014919:4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one; D000093542:Gemcitabine