Annals of Oncology 14: 1264–1269, 2003Original article DOI: 10.1093/annonc/mdg340 © 2003 European Society for Medical Oncology

Background: The aim of this study was to determine the maximum tolerated dose (MTD), toxicity profile and response rate of the oral 5-fluorouracil prodrug UFT (tegafur/uracil) and leucovorin (LV) in combination with irinotecan in patients with advanced or metastatic colorectal cancer. Patients and methods: Patients with histologically proven advanced or metastatic colorectal adenocarcinoma received first-line chemotherapy comprising UFT 250 mg/m2/day and LV 90 mg/day given on days 1 to 14, with escalating doses of irinotecan (200–300 mg/m2) administered intravenously on day 1 of a three-weekly cycle. Eligibility criteria were standard. The MTD was defined as the dose at which>33 % of six patients experienced a dose-limiting toxicity (DLT) during cycle 1. Results: A total of 32 patients were studied. Initially, six patients were treated at each of the irinotecan dose levels (200, 250 and 300 mg/m2) combined with UFT 250 mg/m2/day and LV 90 mg/day. DLTs consisting of grade 3 or 4 diarrhoea and febrile neutropenia were observed in one of 20 patients at 250 mg/m2 and three of six patients at the 300 mg/m2 irinotecan dose level. Having defined the MTD, the 250 mg/m2 dose level was established as the recommended dose (RD) and expanded to 20 patients in whom treatment was generally well tolerated. The overall response rate was 19%, with five patients having a partial response (PR) and 18 stable disease (SD) out of 32 response-evaluable patients