Phase II study of a fixed dose-rate infusion of gemcitabine associated with uracil/tegafur in advanced carcinoma of the pancreas

Background: The objectives of this study were to evaluate the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated with uracil/tegafur (UFT) in patients with advanced adenocarcinoma of the pancreas. Patients and methods: Forty-three chemotherapy-naive patients with adenocarcinoma of the pancreas were included in this phase II study. All of whom had a Karnofsky performance status greater than or equal to50 and bi-dimensionally measurable disease (either advanced non-resectable or metastatic); median age 59 years (range 39-77); male:female ratio 29:14. Eight patients (19%) had locally advanced disease and 35 (81%) distant metastases. Treatment consisted of gemcitabine 1200 mg/m(2) given as a 120-min infusion weekly for 3 consecutive weeks, plus oral UFT 400 mg/m(2)/day (in 2-3 doses per day) on days 1-21, cycles were given every 28 days. Measurements of efficacy included response rate, clinical benefit response, time to disease progression and overall survival. Results: A total of 192 cycles of chemotherapy were delivered with a median of four per patient. There were two complete responses (5%) and 12 partial responses (28%), producing an overall response rate of 33% [95% confidence interval (CI) 16% to 49%]. Thirteen patients (30%) had stable disease, whereas 16 (37%) had a progression. The median time to progression was 6 months and the median overall survival was 11 months. Twenty-five patients (64%, 95% CI 47% to 78%) experienced a clinical benefit response. Grade 3-4 WHO toxicities were: neutropenia in nine patients (21%); thrombocytopenia in four (9%); anaemia in five (12%); diarrhoea in four (9%); and asthenia in one (2%). Conclusions: A fixed dose-rate infusion of gemcitabine associated with UFT was well tolerated and showed promising activity in patients with locally advanced or metastatic carcinoma of the pancreas. This is an appropriate palliative treatment in this setting.