Weekly high-dose 5-fluorouracil and folinic acid in metastatic pancreatic carcinoma: a phase II study of the EORTC GastroIntestinal Tract Cancer Cooperative Group R.E.N. Van Rijswijk a, * , K. Jeziorski b , D.J.TH. Wagener c , J.-L. Van Laethem d , S. Reuse e , B. Baron e , J. Wils f , for the EORTC GastroIntestinal Tract Cancer Cooperative Group a Departments of Hematology/Oncology, University Hospital Maastricht, P. Debyelaan 25, 6202 Maastricht, The Netherlands b Oncology Center Institute, Warsaw, Poland c St Radboud Hospital, University of Nijmegen, The Netherlands d Hopital Universit e Erasme, Brussels, Belgium e EORTC Data Center, Brussels, Belgium f Laurentius Hospital, Roermond, The Netherlands Received 6 November 2003; received in revised form 3 June 2004; accepted 11 June 2004 Available online 4 August 2004 Abstract The aim of the study was to assess the response rate and toxicity of high-dose 24 h infusion of 5-fluorouracil (5FU) in metastatic adenocarcinoma of the pancreas. Patients with measurable disease, performance status 0–2, and no prior chemotherapy were reg- istered to receive cycles of leucovorin (LV) 500 mg/m 2 (or l-LV 250 mg/m 2 over 1 h followed by 5FU 2.6 g/m 2 over 24 h, weekly for 6 weeks, followed by a 2-week rest. The main endpoints were the response rate and toxicity. From 37 patients, 36 were the analysed for toxicity, and 33 were eligible and analysed for response. The median age was 59 years (range 28–74 years), and the median perfor- mance status was 1. Partial response was observed in three patients (9%) (95% Confidential Interval (CI): [2–24]%). Main grade 3/4 National Cancer Institute (NCI) common toxicity criteria toxicities (patients) were diarrhoea (n ¼ 3), vomiting (n ¼ 2) and hand–foot syndrome (n ¼ 5). Median time to progression was 7 weeks (95% CI: [6.4–11.7] weeks) and median survival 19 weeks (95% CI: [12–35] weeks). In conclusion, high-dose 5FU and folinic acid is well tolerated, but has only modest activity in pancreatic cancer. Ó 2004 Elsevier Ltd. All rights reserved. Keywords: Pancreatic neoplasms/drug therapy; Fluorouracil; Leucovorin 1. Introduction Pancreatic cancer is the fourth most common cause of death from malignant disease in Western countries. These tumours account for 3% of all malignancies, but for 5% of all cancer deaths. The disease carries a poor prognosis, the median survival of all patients with tu- mours of the exocrine pancreas being only 4–6 months. Only a few patients are candidates for surgical resection, which is the only possibility for cure [1]. All other pa- tients may be considered for palliative chemotherapy or radiotherapy, the modality of treatment primarily being dependent on the stage of the disease. A large number of chemotherapeutic agents have been investigated in pancreatic cancer, but the results of both single-agents and combination chemotherapy in terms of response rate and overall survival have been disappointing [2,3]. The European Organisation for Research and Treat- ment of Cancer (EORTC) Gastrointestinal Tract Can- cer Cooperative Group (GITCCG) previously initiated studies with cisplatin, ifosfamide, epirubicin and epiru- bicin-based combination chemotherapy [4–8]. Especially in patients with metastatic pancreatic cancer, the toxicity of chemotherapy is of concern, as a decreased performance status and concomitant liver-, * Corresponding author. Tel.: +31-43-3877025; fax: +31-43-3875006. E-mail address: rri@sint.azm.nl (R.E.N. Van Rijswijk). 0959-8049/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2004.06.012 European Journal of Cancer 40 (2004) 2077–2081 European Journal of Cancer www.ejconline.com