Randomized phase II trial of preoperative combined modality chemoradiation for distal rectal cancer.

3535 Background: Potential advantages of preoperative radiotherapy (RT) include increased resectability, sphincter preservation, local control, and overall survival. This randomized phase II study was designed to evaluate, pathologic complete response(pCR) to preoperative combined-modality chemotherapy with 5-fluorouracil (5FU) and RT, or with 5FU, irinotecan (I) and RT in patients with adenocarcinoma of the rectum. METHODS Patients with T3/T4 tumors located 0-9 cm from the dentate line, without distant metastases or extension to the anal canal, were stratified according to clinical staging and were randomized to receive :Arm 1 [(5FU/RT)-CVI 5-FU (225 mg/m2/d, 7 d/wk) + pelvic RT 45.6 Gy (1.23 Gy/bid, ≥6-hour interval) + boost to tumor (9.6 Gy for T3 and 14.4 Gy for fixed T4)]; orArm 2 [(5FU/RT/I -CVI 5-FU (225 mg/m2/d, M-F,) +I(50 mg/m2 once weekly x 4)+ pelvic RT 45 Gy (1.8 Gy/d) + boost to tumor (5.4 Gy for T3 and 9 Gy for fixed T4)]. Surgery was performed 4-10 weeks following completion of therapy. Primary endpoint was pCR, with an expected rate of ≥20%. Secondary endpoints included acute and late normal tissue morbidity, patterns of failure, and complete resection rates. RESULTS 106 patients were enrolled (52 in Arm 1 and 54 in Arm 2); 3 were ineligible or never received protocol therapy, and 103 underwent surgery and were evaluable. Patient characteristics for Arm 1 and Arm 2, respectively, were: median age 56 and 59 years; 84% and 85% Caucasian; 70% and 83% Zubrod score 0; 68% and 75% stage T3; and 54% and 55% N0. Grades 3 and 4 acute hematologic and non hematologic toxicities occurred in 13% and 38%, respectively, in Arm 1 and 12% and 45% in Arm 2. CONCLUSIONS Both regimens were well tolerated with acceptable grade 3/4 toxicities. The pathologic complete response rates of 30% with 5FU/RT and 26% with 5FU/RT/I were higher than in previous reports. Further study of these regimens should be considered. [Table: see text].