Objectives: FOLFIRI is one of the current standard first-line regimens for advanced colorectal cancer, but its administration is onerous. Because the replacement of 2-day-infusional 5-fluorouracil (5-FU) of FOLFIRI with oral tegafur-uracil/leucovorin (UFT/LV) would be highly beneficial for clinical management, we performed a phase I trial using oral UFT/LV and a pharmacokinetic evaluation.
Methods: Treatment consisted of infusional irinotecan (100 mg/m)/l-LV (15 mg/m) and a bolus injection of 5-FU (500 mg/m) on day 1, and oral UFT (300 mg as tegafur/m/d)/LV (75 mg/d) on days 1-5 (level 1), days 1-7 (level 2), or days 1-10 (level 3). Cycles were repeated every 14 days. After determination of the recommended UFT/LV administration period, irinotecan was dose-escalated (level 4: 125 mg/m; level 5: 150 mg/m).
Results: Nineteen patients were enrolled. One dose-limiting toxicity (DLT), grade 4 neutropenia lasting for > or =4 days was observed at level 2. At level 3, one DLT of treatment delay of > or =8 days occurred due to prolonged neutropenia, and 2 patients refused to continue the treatment because of prolonged grade 2 anorexia. Therefore, a 7-day administration of UFT/LV was recommended. No DLT was observed at levels 4 and 5. Pharmacokinetic evaluation suggested continuous exposure to 5-FU by means of oral UFT/LV administration in this combination.
Conclusions: The recommended administration period was 7 days for oral UFT/LV, and the recommended dose of irinotecan was 150 mg/m. A phase II study is ongoing to validate the clinical outcome.