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

Gemcitabine (Gemzar(R)) 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/m(2)) and folinic acid (200 mg/m(2)) 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/m(2), eight received 5-FU 1000 mg/m(2) and two received 5-FU 1250 mg/m(2). The maximum tolerated dose of 5-FU was 1000 mg/m(2). Hepatotoxicity was dose limiting, One patient who received 5-FU 1250 mg/m(2) died as a result of hepatorenal 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/m(2) 5-FU. [(C) 1999 Lippincott Williams & Wilkins].