Fixed-dose rate gemcitabine alone or alternating with FOLFIRI.3 (irinotecan, leucovorin and fluorouracil) in the first-line treatment of patients with metastatic pancreatic adenocarcinoma: An AGEO randomised phase II study (FIRGEM)

{Background: Fluorouracil and irinotecan-based, and gemcitabine-based regimens, are the standard of care in the first-line treatment of patients with metastatic pancreatic cancer. New approaches are needed to improve survival and quality of life. Whether a sequential approach alternating irinotecan, fluorouracil and gemcitabine may be effective and tolerable in patients with metastatic pancreatic cancer is unknown. Methods: In this randomised, multicentre, open-label, phase 2 trial, patients with metastatic pancreatic adenocarcinoma, World Health Organisation (WHO) performance status 0-1, and bilirubin levels <1.5 upper limit of normal values (ULN) were randomised 1: 1 to receive as first-line treatment either FOLFIRI. 3 (irinotecan, leucovorin and fluorouracil) alternating with fixed-dose rate gemcitabine as 2-month periods (FIRGEM, arm A), or fixed-dose rate gemcitabine alone (arm B). Treatment was continued until disease progression or limiting toxicity. The primary end-point was the crude progression-free survival (PFS) rate at 6 months. The study is registered with EudraCT (N degrees 2006-005703-34). Results: Between October 2007 and March 2011, 98 patients were enroled. The observed 6-month PFS rate was 43.5% (95% confidence interval (CI), [28.6-58.4%]) in arm A reaching the Fleming decision rules criteria to reject H0 and 26.1% (95% CI [12.9-39.3%]) in arm B. Objective response rates were 37% (23-51%) in arm A and 10% (1-19%) in arm B. Median PFS (5.0 versus 3.4 months, hazard ratio (HR) = 0.59 [0.38-0.90]) and overall survival (11.0 versus 8.2 months