UFT plus calcium folinate/irinotecan in colorectal cancer

This phase I trial combining UFT plus oral calcium folinate (Orzel) with ir inotecan (CPT-11) (Camptosar)for the treatment of patients with advanced or metastatic colorectal cancer will open shortly, Eligible patients will hav e locally advanced or metastatic colorectal cancer, and they may have recei ved adjuvant chemotherapy (provided it has been completed more than 6 month s prior to study entry), but will have not received any chemotherapy for ad vanced or metastatic disease. The primary objectives of this study will be to determine the side-effect profile, dose-limiting toxicities, and the max imum tolerated dose of this combination, A recommended starting dose for fu ture trials will be defined, Response rates will also be observed as a seco ndary objective, The first cohort of six patients will receive irinotecan 2 00 mg/m(2) by intravenous infusion over 90 minutes on day 1 (the schedule t hat is in general use in Europe). On days 1 to 14, patients will receive UF T 250 mg/m(2)/d and calcium folinate 90 mg/d, both divided into three equal doses. This will be followed by a 1-week rest period with treatment for th e next cycle resumed on day 22, In subsequent cohorts of six patients, UFT and irinotecan will in turn be escalated provided toxicity is acceptable. T he calcium folinate dose will remain fixed at 90 mg/d throughout, The maxim um tolerated dose is defined as that at which dose-limiting toxicities occu r in more than one third of patients. The cohort of patients treated at the dose below the maximum tolerated dose will be expanded to a total of 20 pa tients to fully define the pattern of toxicities and activity of the combin ation.