Phase I trial of gemcitabine (Gemzar®), 24 h infusion 5-fluorouracil and folinic acid in patients with inoperable pancreatic cancer

Abstract

Gemcitabine (Gemzar®) has a significant impact upon survival and quality of life for patients with pancreatic cancer, compared with 5-fluorouracil (5-FU). This phase I study was initiated to define the recommended dose of 5-FU delivered as a 24 h infusion in combination with gemcitabine (1000 mg/m²) and folinic acid (200 mg/m²) in patients with inoperable pancreatic cancer, treated on an outpatient basis. Drugs were administered weekly for 4 weeks out of 6 weeks. Sixteen chemonaive patients (median age 59 years, range 51–66) were enrolled, 15 had stage IV and one stage III disease. The median Karnofsky performance score (KPS) was 70 (range 60–80). Six patients received 5-FU 750 mg/m², eight received 5-FU 1000 mg/m² and two received 5-FU 1250 mg/m². The maximum tolerated dose of 5-FU was 1000 mg/m². Hepatotoxicity was dose limiting. One patient who received 5-FU 1250 mg/m² died as a result of hepato-renal failure. There was one partial response, nine patients had stable disease for more than 3 months and 13 patients had improved KPS. The median time to progressive disease was 31 weeks (range 5–50 weeks). A phase II trial is underway to further assess the activity of this combination at the recommended dose of 750 mg/m² 5-FU.