Annals of Oncology 14:1264-1269, 2003
© 2003 European Society for Medical Oncology
Original Paper |
A phase I/II study of oral uracil/tegafur (UFT), leucovorin and irinotecan in patients with advanced colorectal cancer
1 Cancer Research UK, Department of Medical Oncology, Beatson Oncology Centre, Western Infirmary, Glasgow; 2 Royal Marsden NHS Trust, Gastrointestinal Unit, London and Surrey; 3 Bristol-Myers Squibb Oncology, London, UK 4 University of Leeds and Tom Connors Cancer Research Centre, University of Bradford, Bradford, UK
Received 4 November 2002; revised 24 March 2003; accepted 15 April 2003
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.
Conclusion:
UFT and LV can be safely combined with irinotecan. The RDs for future studies are UFT 250 mg/m2/day and LV 90 mg/day given on days 1–14, with irinotecan 250 mg/m2 administered on day 1, every 3 weeks. This combination is well tolerated and active. Further investigation of UFT and LV in combination with irinotecan is warranted in patients with colorectal cancer.
Key words: chemotherapy, colorectal cancer, irinotecan, leucovorin, tegafur/uracil
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