Phase III trial comparing initial chemoradiotherapy (intermittent cisplatin and infusional 5-FU) followed by gemcitabine vs gemcitabine alone in patients with locally advanced non metastatic pancreatic cancer. Preliminary results.
Résumé
Background: The GITSG studies have shown a greater survival after 5 FU-based chemoradiotherapy (CHRT) than radiotherapy or polychemotherapy alone in patients (pts) with locally advanced non metastatic pancreatic cancer. This randomized trial evaluated whether initial CHRT adds to modern gemcitabine in term of Overall Survival (OS). Methods: Pts with WHO status 0-2, proven adenocarcinoma of the pancreas, without metastasis at CT-scan, and deemed non resectable, were randomized 1:1 between CHRT ( 60 Gy in 6 weeks, 2 Gy/fraction, concomitant with 5-FU, 300 mg/m2/24 h as a continuous infusion, day 1-5 every week and cisplatin, 20 mg/m2/d, day 1-5 at week 1 and 5) or gemcitabine (G) (1000 mg/m2 weekly 7q8w) as induction treatment. Maintenance treatment was G (1000 mg/ m2 weekly 3q4w) in both arms until progression or limiting toxicity. Stratification criteria were: center, WHO status and initial surgery. It was required to include 176 pts to detect an expected change in median OS from 6 to 12 months (bilateral α = 1% and β = 10%). Intent to treat survival analysis used the Logrank test. Results: Between 03/00 and 07/05, 59 pts were randomized to CHRT and 60 to G. Median follow-up at the 05/05 was 16 months. Pt characteristics were well balanced (CHRT/G) with mean age (60.1/62.7 year), sex ratio (1/ 1.4) and WHO status ( 0-1: 88%/73%, 2: 9%/23%). During the induction phase, more than 75% of the planned dose was completed in 81.4% of pts for radiotherapy, 52.5% for 5-FU and 50.8% for cisplatin and 76.7% of pts in the G arm. In CHRT and G arms, OS at 6 and 12 months were respectively 78/82% and 24/51%, with a median survival of 8.4/14.3 months (stratified log-rank p = 0.014). CHRT or G related toxicities during induction phase were grade 3/4 leukopenia (17%/10%), thrombopenia (8.5%/0%), non-haematological toxicity (37%/ 17%) with diarrhea (7%/0% ), cutaneous toxicity (0%/3%). One treatment-related death was observed in the CHRT arm (aplasia). Conclusion: Study was stopped before the planned inclusion due to lower survival with initial CHRT when compared to G alone. Reasons explaining this difference are under investigation.