Activity of gemcitabine and continuous infusion fluorouracil in advanced pancreatic cancer

Background/Objectives: Gemcitabine has been shown to improve survival and quality of life parameters compared to fluorouracil alone in advanced pancreatic cancer [J Clin Oncol 1997;15:2403-2413]. However, fluorouracil was given as a weekly bolus in that study and other administration schedules might be more effective. The objective of this trial was to determine the activity and toxicity of gemcitabine in combination with continuous infusion (CI) fluorouracil in advanced pancreatic cancer. Patients and Methods: Chemotherapy-naïve patients with measurable advanced adenocarcinoma of the pancreas were treated with gemcitabine 1,000 mg/m² intravenously weekly × 3 followed by 1 week of rest every 4 weeks and 200 mg/m²/day CI fluorouracil until disease progression or limiting toxicity. Results: Twenty-five patients were evaluable for response and toxicity. Objective partial responses were documented in 5 patients (20%; 95% confidence interval 6.8-40.7%) and disease stabilization or minor responses in 13 patients (52%; 31.3-72.2%). Toxicity was mild with grade 2/3 leucopenia in 26%, stomatitis in 15%, nausea in 6%, diarrhea in 3%, and hand-foot syndrome in 2% of the treatment cycles. In 3 patients a catheter thrombus occurred and in 1 patient the treatment had to be stopped due to asthenia. The performance status improved in 39% of the patients and 65% benefitted in terms of a decrease in pain intensity or consumption of analgesics. Conclusion: This phase II trial confirms a significant antitumor activity and a beneficial clinical effect of gemcitabine plus CI fluorouracil in advanced pancreatic cancer. The combination is well tolerated and it will have to be shown whether oral fluoropyrimidines can increase the practicability of this treatment without impairing efficacy.