Importance:Several studies have explored the efficacy and toxic effects of concurrent 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) with or without oxaliplatin in the neoadjuvant setting. Addition of oxaliplatin to 5-FU or capecitabine elicited similar outcomes but with significantly increased toxic effects; however, there is a need for randomized clinical trials comparing 2 CRT regimens for patients receiving CRT in the adjuvant setting. Objective:To explore the efficacy and toxic effects of oxaliplatin combined with postoperative concurrent capecitabine and radiotherapy (RT) for pathological stage II and III rectal cancer. Design, Setting, and Participants:This multicenter randomized clinical trial enrolled patients from 7 centers in China between April 1, 2008, and December 30, 2015. Patients with pathologically confirmed stage II and III rectal cancer were randomized (1:1) to receive concurrent CRT with capecitabine or capecitabine plus oxaliplatin. Analysis was conducted from December 31, 2019, to March 15, 2020. Interventions:RT comprised 45 to 50 Gy in 25 fractions of 1.8 to 2.0 Gy over 5 weeks. In the capecitabine with RT group, concurrent chemotherapy included 2 cycles of capecitabine (1600 mg/m2) on days 1 to 14 and 22 to 35. The capecitabine and oxaliplatin with RT group received identical postoperative RT to that in the capecitabine with RT group combined with capecitabine (1300 mg/m2) on days 1 to 14 and 22 to 35 and a 2-hour infusion of oxaliplatin (60 mg/m2) on weeks 1, 2, 4, and 5. Patients in both groups received adjuvant chemotherapy (capecitabine or fluorouracil and oxaliplatin) after CRT. Main Outcomes and Measures:The primary end point was 3-year disease-free survival (DFS). Results:A total of 589 patients (median [IQR] age, 55 [47-52] years; 375 [63.7%] men and 214 [36.3%] women) were enrolled, including 294 patients randomized to the capecitabine with RT group and 295 patients randomized to the capecitabine and oxaliplatin with RT group. Median (IQR) follow-up was 68 (45-96) months. Most patients had stage III disease (574 patients [75.9%]). Three-year DFS was 76.3% for the capecitabine with RT group and 74.1% for the capecitabine and oxaliplatin with RT group, and 5-year DFS was 72.0% for the capecitabine with RT group and 71.1% for the capecitabine and oxaliplatin with RT group (hazard ratio [HR], 1.07; 95% CI, 0.79-1.44; P = .68). There was no significant difference between groups in overall survival (HR, 0.93; 95% CI, 0.64-1.34; P = .70) or local recurrence (HR, 0.61; 95% CI, 0.31-1.22; P = .16). More grade 3 and 4 acute toxic effects were observed in the capecitabine and oxaliplatin with RT group than in the capecitabine with RT group (114 patients [38.6%] vs 84 patients [28.6%]; P = .01). Conclusions and Relevance:This randomized clinical trial found that addition of oxaliplatin to capecitabine-based postoperative CRT did not improve the efficacy of treatment but increased the risk of severe acute toxic effects. This finding highlights the basic role of postoperative capecitabine with RT for patients with locally advanced rectal cancer. Trial Registration:ClinicalTrials.gov Identifier: NCT00714077.

e15006 Background: To present an interim analysis of a phase III trial comparing short-course radiotherapy followed by chemotherapy with long-course chemoradiotherapy in locally advanced rectal cancer. Methods: Patients with distal or middle third, MRI diagnosed cT3-T4 or N+ rectal adenocarcinomas were randomized to either 5 x 5 Gy and 4 courses of CAPOX (experimental group) or 50 Gy delivered in 25 fractions given concurrently with capecitabine (control group). Total mesorectal excision (TME) in both groups was performed 6-8 weeks after neoadjuvant treatment. This is an interim analysis of acute toxicities for the first 127 patients who finished neoadjuvant therapy, as well as the pCR and surgical complications for the first 100 patients who received surgery. Results: From 08/30/2015 to 12/11/2016, 63 patients in experimental group and 64 in control group from 10 Chinese hospitals were analyzed. During preoperative treatment, any acute toxicities were 100% in both groups and grade III-IV 19.0% vs. 6.3% ( p= 0.03) in experimental group and control group, respectively. Full-dose completion rates of planned neoadjuvant treatment were 88.9% and 93.7% in each group ( p= 0.33), respectively. After median duration of 7 weeks and 9 weeks in experimental group and control group, TME was performed. Among the 100 patients who have finished surgery, 94.1% and 89.8% in experimental and control group had R0 resection ( p= 0.426), while 21.6% and 6.1% of them achieved pCR ( p= 0.026), respectively. There were 8 patients in experimental group diagnosed as clinical CR and refused to further radical surgery, while, none in control group ( p= 0.003). The incidences of surgical complications were similar between two groups (experimental 29.1% vs. control 26.5%; p= 0.748), with perineal healing delay as the main reason. Conclusions: The acute toxicity and surgical complication were acceptable and comparable in both groups, however, the people in experimental group showed a significantly clinical and pathological response. The short-course irradiation and consolidation chemotherapy maybe an alternative standard of care, though the final result is in prospect. Clinical trial information: NCT02533271.