Phase II study of biweekly gemcitabine followed by oxaliplatin and simplified 48-h infusion of 5-fluorouracil/leucovorin (GOFL) in advanced pancreatic cancer

Purpose: To evaluate the efficacy and safety profile of a triplet regimen consisting of gemcitabine, oxaliplatin, and infusional fluorouracil and leucovorin (LV) in advanced pancreatic carcinoma (APC). Patients and methods: Chemotherapy-na?ve patients with histo-/cytologically proven unresectable APC, and bi-dimensionally measurable diseases were eligible. Treatment consisted of fixed-dose rate (10 mg/m2/min) infusion of 800 mg/m2 gemcitabine followed by 2-h infusion of 85 mg/m2 oxaliplatin and then 48-h infusion of fluorouracil and LV (3,000 and 300 mg/m2, respectively) every 2 weeks (the GOFL regimen). The primary end-point was objective response rate. Results: Forty-five patients were enrolled and received a median of seven [95% confidence interval (CI) 6.4-8.8] cycles of treatment. On intent-to-treat analysis, the overall response and disease-control rates were 33.3% (95% CI 21.4-48.0%) and 68.9% (95% CI 54.8-83.0%), respectively. Clinical benefit response was observed in 46.2% of initially symptomatic patients. The median time-to-tumor progression and overall survival were 5.1 (95% CI 4.0-6.3) months and 8.7 (95% CI, 6.1-11.3) months, respectively. Major grade 3-4 toxicities were neutropenia (28.9%, with 4.4% complicated with fever), peripheral sensory neuropathy (15.6%), nausea/vomiting (13.3%), and diarrhea (6.7%). Conclusions: The triplet regimen is feasible and exhibits promising activity against APC, deserving further exploration. ? 2009 Springer-Verlag.