Randomized Double-Blind Phase II Trial Comparing Gemcitabine Plus LY293111 Versus Gemcitabine Plus Placebo in Advanced Adenocarcinoma of the Pancreas

Background: LY293111 (LY) is a novel oral anticancer agent with leukotriene B-4 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. Patients and Methods: Chemotherapy-naive patients with histologically confirmed locally advanced or metastatic adenocarcinoma of the pancreas were randomly assigned to gemcitabine 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle and continuously administered LY 600 mg twice daily or gemcitabine 1000 mg/m(2) 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.