Background
Phase III RCT (RTOG 9704). 538 patients with resected pancreatic cancer (head, body, or tail). All patients received 5-FU-based CRT (50.4 Gy + continuous infusion 5-FU). Randomized to gemcitabine or 5-FU before and after CRT (the CRT itself was identical in both arms).
Interventions and follow up
Arm A: Gemcitabine 1,000 mg/m² weekly × 3 before CRT, then gemcitabine × 3 months after CRT
Arm B: 5-FU 250 mg/m² continuous infusion before CRT, then 5-FU × 3 months after CRT
Primary endpoint: Overall survival
mFollow up: 5.9 year
Arm B: 5-FU 250 mg/m² continuous infusion before CRT, then 5-FU × 3 months after CRT
Primary endpoint: Overall survival
mFollow up: 5.9 year
Results
Both arms: 50.4 Gy in 28 fractions + continuous infusion 5-FU during RT
mOS (head tumors, primary analysis): 20.5 months (gemcitabine) vs 16.9 months (5-FU), HR 0.82, P=.09 — not significant
3-yr OS (head tumors): 31% vs 22%
mOS (all patients): 18.8 vs 16.7 months, P=.34
mOS (head tumors, primary analysis): 20.5 months (gemcitabine) vs 16.9 months (5-FU), HR 0.82, P=.09 — not significant
3-yr OS (head tumors): 31% vs 22%
mOS (all patients): 18.8 vs 16.7 months, P=.34
Adverse events
Main adverse events: Grade ≥3 hematologic toxicity higher with gemcitabine (58% vs 9%). Grade ≥3 GI toxicity: 8% (gem) vs 14% (5-FU).
Conclusions
Gemcitabine-based adjuvant therapy trended toward improved survival versus 5-FU, particularly in pancreatic head tumors (HR 0.82), but did not reach statistical significance. The trial supported using gemcitabine in the peri-CRT period and provided benchmark survival data for adjuvant CRT trials.
Key Limitations
Key Limitations: Primary endpoint (OS in head tumors) was not met. The CRT was identical in both arms — this was not a CRT vs. no-CRT comparison. Hematologic toxicity was substantially higher with gemcitabine. Trial predated CONKO-001, ESPAC-3, and PRODIGE-24, which have since defined systemic chemo without routine CRT as standard. The role of the CRT backbone was not tested in this design.
Clinical Context
RTOG 9704 supported gemcitabine as a preferred systemic partner for peri-CRT therapy in resected pancreatic cancer in the US. However, the field has largely moved toward systemic-only adjuvant approaches. Modern US patterns reserve adjuvant CRT for margin-positive (R1) resections or as part of protocol studies.
References