Neoadjuvant radiotherapy ± tegafur-uracil plus leucovorin in rectal adenocarcinoma: Final results of a French multicenter phase III study.

4104 Background: Neoadjuvant chemoradiotherapy (CRT) with tegafur-uracil (UFT) plus leucovorin (LV) has shown promising results in patients with rectal adenocarcinoma (RAC). We therefore conducted a phase III trial to compare neoadjuvant CRT with UFT/LV versus radiotherapy (RT) alone. METHODS One hundred seventy seven pts with RAC stage T3 (T4 if anal extension) N<2, M0 were randomized to either RT alone (RT) (1.8 Gy/d, 45 G total) 5 days/w for 5 weeks or combined to CT (CRT) with daily UFT 300 mg/m2 plus leucovorin 75 mg for 5 weeks. TME surgery was performed 6-8 weeks after treatment. Adjuvant CT permitted at investigator discretion. Primary endpoint was pathological complete response rate (pCR), secondary endpoints included downstaging, QOL, sphincter preservation, recurrence rates, disease-free and overall survival. RESULTS Of 177 pts, 87 pts were allocated to RT and 90 to CRT. Compliance: RT dose intensity 98.8 % (n=86) in RT arm vs 95.6 % (n=86) in CRT arm with UFT mean dose 295.7 ± 19.8 mg/m2. 172 pts underwent surgery (97.2%), 5 pts were not resected (4 liver and 1 lung metastases plus 1 CVA). Both RT and CRT were well tolerated. No neutropenia and only 1 grade IV diarrhea in the CRT arm were observed. Treatment related death occurred in 4 patients, 3 in the RT arm and 1 in the CRT arm respectively. With a median follow-up at 22.3 mo, median OS is not yet reached. CONCLUSIONS Neoadjuvant radiotherapy combined with UFT increases significantly the pCR rate with an acceptable toxicity. Further survival data will be presented. This is the first randomized study of neoadjuvant CRT highlighting the improvement of the pCR rate with UFT. [Table: see text] [Table: see text].