Phase I/II Study of Preoperative Chemoradiotherapy With TEGAFIRI for Locally Advanced Rectal Cancer.

INTRODUCTION: Chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer; however, the optimal chemotherapy sequence to administer simultaneously with radiotherapy remains unclear. We conducted a phase I/II study to test a new regimen, TEGAFIRI (combination tegafur, uracil [UFT], leucovorin [LV], irinotecan), for patients with locally advanced rectal cancer.

PATIENTS AND METHODS: A total of 22 patients with locally advanced lower rectal adenocarcinoma were enrolled in the present study. The radiation dose was 50.4 Gy in 28 fractions. UFT (300 mg/m2 /d) and LV (75 mg/body weight/d) were administered orally 3 times daily. Irinotecan was administered as an intravenous infusion at 3 escalating dose levels. The initial dose was 50 mg/m2 (level 1; n = 7), the intermediate was 70 mg/m2 (level 2; n = 8), and the maximum was 80 mg/m2 (level 3; n = 7). The drug was administered on days 1, 15, 29, and 43.

RESULTS: Dose-limiting toxicity was not observed at any dosing level. The most frequent adverse event was leukopenia (50%), followed by diarrhea (45.5%), anal pain (31.8%), and neutropenia (27.3%). All were well-managed with the appropriate drugs. The total pathologic complete response rate was 22.7%, and the proportion of good responders was 28.6%, 50%, and 71.4% at levels 1, 2, and 3, respectively. None of the patients experienced local recurrence. The 5-year relapse-free and overall survival rates were 80.4% and 80.8%, respectively.

CONCLUSION: TEGAFIRI is a promising CRT regimen that results in marked tumor regression and good local control. Moreover, its adverse events are well-tolerated.