Pre-operative chemoradiotherapy with UFT and Leucovorin in patients with advanced rectal cancer: A phase II study

Purpose: The aim this study was to determine the pathologic complete response (pCR) rate defined as tumor regression grade 1 (TRG1) and toxicity profile of the combination of high-dose pre-operative radiotherapy and simultaneous UFT/leucovorin (LV) in patients with locally advanced rectal cancer. Materials/methods: Eligibility included biopsy proven rectal adenocarcinoma; T3-T4 N0-N2; performance status <2 (ECOG) and adequate blood, hepatic and renal function. Treatment consisted of radiotherapy 54 Gy at 1.8 Gy/day and UFT 300 mg/m²/day and LV 60 mg/day, given simultaneously daily for 6 weeks. Surgery was performed within 4-6 weeks period after chemoradiotherapy. Patients who did not achieve TGR1 were to receive 4 cycles of adjuvant UFT/LV on days 1-28, every 5 weeks. Results: Sixty-eight patients were included. All but one received full dose of radiation and 62 had the total planned pre-operative UFT/LV dose. Grade 3 toxicities were diarrhea 7% and proctitis 3%. Complete resection was achieved in 62 patients (91%). Tumor regression grade 1 (TRG1) was seen in 11 patients (16%). Forty-eight patients received adjuvant UFT/LV. Grade 3 toxicity during adjuvant UFT/LV included diarrhea 12%, asthenia 4%, neutropenia 2%, and hand-foot syndrome 2%. The 3-year disease-free survival was 71%. Conclusions: Simultaneous high-dose pre-operative localized radiation therapy concurrent with UFT/LV is feasible and has a low toxicity profile. This schedule is highly effective and merits further investigation.