title: Randomized double-blind phase II trial comparing gemcitabine plus LY293111 versus gemcitabine plus placebo in advanced adenocarcinoma of the pancreas.
abstract: BACKGROUND
  LY293111 (LY) is a novel oral anticancer agent with leukotriene B4 receptor antagonist and peroxisome proliferator-activated receptor gamma agonist properties, producing promising results alone and in combination with gemcitabine in pancreatic cancer xenograft models. A phase I study proved that the combination (gemcitabine plus LY) is safe and well tolerated.
  
  
  METHODS
  Chemotherapy-naive patients with histologically confirmed locally advanced or metastatic adenocarcinoma of the pancreas were randomly assigned to gemcitabine 1000 mg/m on days 1, 8, and 15 of a 28-day cycle and continuously administered LY 600 mg twice daily or gemcitabine 1000 mg/m on days 1, 8, and 15 of a 28-day cycle and daily oral placebo. Arms were balanced for Eastern Cooperative Oncology Group performance status and disease stage. The primary end point was 6-month survival; secondary objectives include response rate (RR), progression-free survival, and overall survival.
  
  
  RESULTS
  Six-month survival was not different between groups (P>0.2, 1-sided); progression-free survival and RR were not different (P>0.05, 2-sided). RR was also not impacted. LY did not increase grades 3-4 hematologic toxicities, but was associated with a trend toward more, grades 3-4 diarrhea.
  
  
  CONCLUSIONS
  These results do not demonstrate any benefit to adding LY to gemcitabine in unpretreated patients with advanced pancreatic carcinoma.
authors: Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA. wasif.saif@yale.edu
authors: Muhammad Wasif
authors: MW
authors: Saif
authors: H
authors: H
authors: Oettle
authors: W L
authors: WL
authors: Vervenne
authors: J P
authors: JP
authors: Thomas
authors: G
authors: G
authors: Spitzer
authors: C
authors: C
authors: Visseren-Grul
authors: N
authors: N
authors: Enas
authors: D A
authors: DA
authors: Richards
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D014481:United States; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D001565:Benzoates; C094099:LY 293111; D018102:Receptors, Leukotriene B4; D003841:Deoxycytidine; D000093542:Gemcitabine