FOLFIRI.3 (CPT-11 plus folinic acid plus 5-FU) alternating with gemcitabine or gemcitabine (G) alone in patients (pts) with previously untreated metastatic pancreatic adenocarcinoma (MPA): Results of the randomized multicenter AGEO phase II trial FIRGEM.

4018 Background: CPT-11 showed modest activity and tolerability in MPA. We developed a new strategy to improve efficacy and tolerability of CPT-11 based regimen in MPA pts. Methods: Chemotherapy-naive pts with histologically proven MPA, bilirubin levels < 1.5 ULN and performance status (PS) 0-1 were randomized in a phase II trial to receive either FOLFIRI.3 (CPT-11 90 mg/m2 as a 60-min infusion on day (D) 1, leucovorin 400 mg/m2 as a 2-hr infusion on day 1, followed by 5-FU 2000 mg/m2 as a 46-hr infusion and CPT-11 90 mg/m2, repeated on D3, at the end of the 5-FU infusion, every 2 weeks) for 2 months alternarting with G (1000 mg/m² at a fixed dose rate of 10 mg/m²/min on D1, D8, D15, D29, D36 and D43) for 2 months (arm A) or G alone (arm B). Using Fleming design the primary end point was rate of progression free survival (PFS) at 6 months from (H0) 25% over (H1) 45% needing to include 49 pts/arm. Results: Between 2007 and 2011, 98 pts were enrolled (males: 59, median age: 62 years, PS 0: 32%). Median foll...