Background: The primary endpoint analysis of RTOG 0247 showed that preoperative pelvic RT plus C + O achieved a pathologic complete response rate (pCR) pre-specified threshold (21%) to merit further study, whereas the RT+ C + I arm did not (10%) (ASCO 2008). This current analysis reports on the secondary efficacy endpoints. Methods: A randomized phase II trial evaluated preoperative RT (50.4 Gy in 1.8 Gy fractions) with (1) concurrent C (1,200 mg/m²/d orally M-F during RT) and I (50 mg/m² IV weekly x 4 doses) (Arm 1), and with (2) concurrent C (1,650 mg/m²/d orally M-F during RT) and O (50 mg/m² IV weekly x 5 doses) (Arm 2) in patients with clinical stage T3 or T4 rectal cancer ² 12 cm from the anal verge. Surgery was performed 4-8 weeks following completion of chemoradiation. Four to 6 weeks after surgery, adjuvant chemotherapy (O 85 mg/m²; leucovorin 400 mg/m² IV over 2 hours; 5FU 400 mg/m² IV bolus; 5FU 2400 mg/m²/46 hr infusion) was administered every 2 weeks x 9 cycles. Disease-free (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Distant failure (DF), and second primary failure (SPF) were estimated by the cumulative incidence method. Results: 104 patients (median age 57, min-max: 27-78); 32% female were treated. Patient characteristics were similar for both arms. Median follow-up for the RT+C+I arm was 3.77 (min-max: 0.19-5.23) and for the RT+C+O arm was 3.97 years (min-max: 0.44-5.15). The 4-year DFS, OS, DF, and SPF estimates for each arm are shown in the table. Conclusions: In addition to achieving the primary endpoint goal of high pCR, RT+C+O exhibited favorable activity as demonstrated by secondary efficacy endpoints. Although RT+C+I failed to achieve the pre-specified pCR goal, this regimen demonstrated a consistent trend of favorable activity by secondary efficacy endpoints.

Abbreviations: No. pts, number of patients; TF, total failures; TD, total deaths; 4y, 4-year.