Phase I/II study of gemcitabine as a fixed dose rate infusion and S-1 combination therapy (FGS) in gemcitabine-refractory pancreatic cancer patients

Purpose: There is no standard regimen for gemcitabine (Gem)-refractory pancreatic cancer (PC) patients. In a previous phase II trial, S-1 was found to exhibit marginal efficacy. Gem administration by fixed dose rate infusion of 10 mg/m ²/min (FDR-Gem) should maximize the rate of intracellular accumulation of gemcitabine triphosphate and might improve clinical efficacy. We conducted the phase I/II of FDR-Gem and S-1 (FGS) in patients with Gem-refractory PC. Methods: The patients received FDR-Gem on day 1 and S-1 orally twice daily on days 1-7. Cycles were repeated every 14 days. Patients were scheduled to receive Gem (mg/m ²/week) and S-1 (mg/m ²/day) at four dose levels in the phase I: 800/80 (level 1), 1,000/80 (level 2), 1,200/80 (level 3) and 1,200/100 (level 4). Forty patients were enrolled in the phase II study at recommended dose. Results: The recommended dose was the level 3. In the phase II, a partial response has been confirmed in seven patients (18%). The median overall survival time and median progression-free survival time are 7.0 and 2.8 months, respectively. The common adverse reactions were anorexia, leukocytopenia and neutropenia. Conclusion: This combination regimen of FGS is active and well tolerated in patients with Gem-refractory PC.