Capecitabine, Oxaliplatin, and Irinotecan (XELOXIRI) as Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

Purpose: This study describes the efficacy and safety of irinotecan and oxaliplatin in combination with capecitabine (XELOXIRI) as a neoadjuvant chemotherapy (NAC) regimen for patients with locally advanced rectal cancer (LARC). Methods: From January 2019 through December 2022, 68 LARC patients treated with XELOXIRI were enrolled in the study. XELOXIRI is administered in a three-week cycle consisting of oxaliplatin 70-110 mg/m2 IV for >120 min on day 1; irinotecan 120-160 mg/m2 IV for 90 min on day 1; and capecitabine 700-1100 mg/m2 orally twice daily for 14 days followed by 7 days off. Sixteen cases were treated with combined radiotherapy, including 8 with long-course radiotherapy and 8 with short-course radiotherapy. The efficacy was evaluated based on pelvic MRI (including TNM stage, CRM, and EMVI status), tumor downstaging rate (to ypT0-2N0M0), pCR rate, R0 resection rate, DFS, and OS, and the safety was assessed according to the incidence of adverse events. Results: Sixty-six people had surgery; the R0 resection rate was 100%, and the rate of anal preservation was 97%. The tumor downstaging rate (to ypT0-2N0M0) in the entire group was 53.0%, and the pCR rate was 12.1%. In the XELOXIRI alone group (N = 47), the tumor downstaging rate was 55.3%, and the pCR rate was 12.8%. In the group receiving radiotherapy (N = 16), the tumor downstaging rate was 56.3%, and the pCR rate was 12.5%. In the whole group, the 3-year DFS was 89.0%, and the 3-year survival rate was 98.5%. The 3-year DFS of the XELOXIRI and XELOXIRI + RT groups was 89.9% and 87.2%, respectively. The most frequent grade 3–4 preoperative toxic reactions were neutropenia (8.8%), diarrhea (4.4%), and anemia (2.9%). All adverse events were tolerable. Conclusions: Neoadjuvant chemotherapy with XELOXIRI appears to be feasible and efficacious for patients with LARC. Although neoadjuvant XELOXIRI alone did not yield our expected pCR rate as NAC for LARC, tumor downstaging, R0 resection, sphincter preservation, local recurrence rate, 3-year DFS, OS, and safety were all satisfactory.