Background
Phase III RCT included 126 patients with newly diagnosed, symptomatic, locally advanced or metastatic pancreatic adenocarcinoma. First-line setting.
Interventions and follow up
Arm A: Gemcitabine 1000 mg/m² IV weekly x7, 1 wk rest, then D1,8,15 q4wk
Arm B: 5-FU 600 mg/m² IV weekly
Primary endpoint: Clinical benefit response (composite of pain, performance status, weight); secondary: ORR, OS, time to progression
mFollow up: NR
Arm B: 5-FU 600 mg/m² IV weekly
Primary endpoint: Clinical benefit response (composite of pain, performance status, weight); secondary: ORR, OS, time to progression
mFollow up: NR
Results
Clinical benefit response: 23.8% vs 4.8%, arm A vs B (P=.0022)
mOS: 5.65 vs 4.41 mo (P=.0025)
12-mo OS: 18% vs 2%
mOS: 5.65 vs 4.41 mo (P=.0025)
12-mo OS: 18% vs 2%
Adverse events
Hematologic (grade ≥3, A vs B): neutropenia 25.9% vs 4.9%, anemia 9.7% vs 0%
Non-hematologic (grade ≥3, A vs B): nausea/vomiting 9.5% vs 3.2%; gemcitabine generally well tolerated
Non-hematologic (grade ≥3, A vs B): nausea/vomiting 9.5% vs 3.2%; gemcitabine generally well tolerated
Conclusions
Gemcitabine provided superior clinical benefit response and a modest survival advantage over bolus 5-FU, establishing it as a first-line standard for advanced pancreatic cancer.
Key Limitations
Small sample size; novel clinical benefit response primary endpoint rather than survival. Bolus 5-FU comparator now considered suboptimal. Absolute survival gains modest.
Clinical Context
This landmark trial established gemcitabine as the backbone of pancreatic cancer therapy for over a decade. Gemcitabine-based regimens (with nab-paclitaxel) and FOLFIRINOX are current ESMO-endorsed first-line standards depending on performance status.