A Randomized Phase 2 Trial of Consolidation Chemotherapy After Preoperative Chemoradiation Therapy Versus Chemoradiation Therapy Alone for Locally Advanced Rectal Cancer: KCSG CO 14-03

Purpose Preoperative chemoradiation therapy (CRT) followed by total mesorectal excision (TME) in locally advanced rectal cancer is the standard of care. To date, the role of consolidation chemotherapy after CRT has rarely been addressed through randomized trials. This study aimed to evaluate the efficacy of CRT followed by consolidation chemotherapy compared with CRT alone. Methods and Materials This study enrolled patients with adenocarcinoma of the rectum and cT3 or cT4 disease with any N category and no metastasis. In arm A (control arm), we planned CRT (50.4 Gy in 28 fractions) with capecitabine followed by TME. In arm B, 2 cycles of capecitabine and oxaliplatin were administered 1 week after the completion of CRT before TME (capecitabine, 1700 mg/m2 per day from day 1 to 14, and oxaliplatin, 100 mg/m2 on day 1, every 3 weeks). The downstaging rate (the proportion of ypT0 to ypT2 and ypN0M0) was the primary endpoint, which was to be tested with a 1-sided type I error of 15% and with 85% power. Results From September 2014 to February 2016, 110 patients (56 in arm A and 54 in arm B) were randomized and 108 (55 in arm A and 53 in arm B) started CRT. TME was conducted per protocol in 96 patients (52 in arm A and 44 in arm B). In arms A and B, downstaging was achieved in 21.2% and 36.4% (P = .077), respectively, and the pathologic complete response rate was 5.8% and 13.6% (P = .167), respectively. Grade ≥3 adverse events occurred in 3.6% of patients in arm A and 9.4% of patients in arm B during the preoperative treatment phase and in 1.9% and 9.0%, respectively, during the postoperative recovery phase. Conclusions Consolidation chemotherapy with 2 cycles of capecitabine and oxaliplatin demonstrated a marginal improvement in the downstaging rate. However, a phase 3 trial of this strategy is discouraged because of the high dropout rate and safety issues.