Capecitabine, oxaliplatin, radiotherapy, and excision (CORE) in patients with MRI-defined locally advanced rectal adenocarcinoma: Results of an international multicenter phase II study

Abstract

3528 Background: The addition of chemotherapy to preoperative radiotherapy (RT) may reduce distant recurrence and increase tumor resectability. The CORE study evaluated oxaliplatin, capecitabine, and RT (XELOX-RT) followed by total mesorectal excision (TME), then adjuvant XELOX in patients (pts) with MRI-defined locally advanced rectal cancer. Methods: MRI inclusion criteria: tumor beyond mesorectal fascia, tumor ≤2 mm from mesorectal fascia, or T3/4 tumor <5 cm from anal verge. Chemoradiation (CRT) was 45 Gy RT (1.8 Gy/dose) 5 days/wk for 5 wks, weekly oxaliplatin 50 mg/m2, and twice-daily capecitabine 825 mg/m2 on each day of RT. Surgery was 6–8 wks after completing XELOX-RT. Pts with R0-R1 resection were to receive XELOX for 6 cycles. Central radiologic and histopathologic review were key study components. Processes to determine histopathologic response and circumferential resection margin (CRM) were predefined. The primary endpoint was pCR rate (planned n=70 evaluable pts). Results: Between July 2003 and Dec 2004, 87 pts were enrolled; 85 pts received XELOX-RT and 79 had TME. Seventy pts (82%) had R0-R1 resection, with a 67% R0 rate (n=57) by Quirke methodology (CRM >1 mm). The pCR rate was 13% (10/78 pts assessable for tumor response; 95% CI, 5.46–20.34%). Tumor regression grading showed excellent response in 35% and poor response in 64% of pts. Of 60 pts evaluated by central MRI review for response by RECIST, the overall response rate was 70% (7% complete; 63% partial response). Preoperative grade (G) 3/4 adverse events (% of pts; evaluable n=85) included diarrhea 16% (12% G3), sensory neuropathy 1% (G3), neutropenia 1% (G3), and hand-foot syndrome 1% (G3). More than 90% of pts received full dose radiotherapy. Conclusions: Significant tumor regression and a high R0 resection rate were achieved using a CRT regimen of preoperative oxaliplatin, capecitabine, and 45 Gy RT, with acceptable toxicity. Central histopathologic and radiologic review data, together with safety and efficacy results for both preoperative CRT and postoperative chemotherapy, will be presented. [Table: see text]