Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, People's Republic of China.
Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, People's Republic of China.
Clin Colorectal Cancer. 2019 Dec;18(4):238-244. doi: 10.1016/j.clcc.2019.07.001. Epub 2019 Jul 11.
Although neoadjuvant chemo-radiotherapy (CRT) achieves low local recurrence rates in locally advanced rectal cancer (LARC), it raises a lot of concerns about long-term anal and sexual functions. We explored the efficacy of preoperative chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in patients with LARC.
Patients with LARC evaluated by pelvic magnetic resonance imaging (MRI) were enrolled in this trial. All received 4 to 6 cycles of mFOLFOXIRI. MRI was performed to assess clinical response after chemotherapy. Patients with mesorectal fascia-positive or ycT4a/b after re-evaluation would receive radiation before surgery, whereas responders would have immediate total mesorectal excision (TME). Adjuvant chemotherapy with mFOLFOX6 (folinic acid, 5-fluorouracil, and oxaliplatin) was recommended. The primary endpoint was the proportion of tumor downstaging to ypTNM. The secondary endpoints were pathologic complete response rate (pCR), 3-year disease-free survival rate, and safety.
Overall, 106 patients were enrolled and received neoadjuvant mFOLFOXIRI chemotherapy. A total of 103 participants underwent TME surgery. Among 103 patients who completed at least 4 cycles of preoperative chemotherapy, 2 received short-term radiation before TME, and 12 underwent long-term CRT after MRI evaluation. The pCR rate was 20.4%, and the tumor downstaging rate was 42.7%. Among patients without preoperative long-term radiotherapy, the pCR rate and tumor downstaging rate were 17.4% and 41.3%, respectively. Among the per-protocol population, the tumor downstaging rate was 48.1%, and the pCR rate was 20.3%. The chemotherapy-related toxicity was well-tolerated.
Neoadjuvant chemotherapy with mFOLFOXIRI and selective radiation does not seem to compromise outcomes in LARC. It could be a reasonable alternative to CRT in previously untreated patients with LARC.
新辅助放化疗（CRT）虽然能降低局部晚期直肠癌（LARC）的局部复发率，但对长期肛门和性功能仍存在诸多顾虑。本研究旨在探讨 mFOLFOXIRI（亚叶酸钙、5-氟尿嘧啶、奥沙利铂和伊立替康）术前化疗在 LARC 患者中的疗效。
经盆腔磁共振成像（MRI）评估的 LARC 患者纳入本试验。所有患者均接受 4-6 个周期的 mFOLFOXIRI 治疗。化疗后行 MRI 评估临床反应。再次评估后系膜筋膜阳性或 ycT4a/b 的患者将接受术前放疗，而有反应的患者则立即行全直肠系膜切除术（TME）。建议行 mFOLFOX6（亚叶酸钙、5-氟尿嘧啶和奥沙利铂）辅助化疗。主要终点为肿瘤降期至 ypTNM 的比例。次要终点为病理完全缓解率（pCR）、3 年无病生存率和安全性。
共纳入 106 例患者接受新辅助 mFOLFOXIRI 化疗。103 例患者接受 TME 手术。在至少完成 4 个周期术前化疗的 103 例患者中，2 例在 TME 前接受短期放疗，12 例在 MRI 评估后行长期 CRT。pCR 率为 20.4%，肿瘤降期率为 42.7%。未行术前长期放疗的患者 pCR 率和肿瘤降期率分别为 17.4%和 41.3%。在符合方案人群中，肿瘤降期率为 48.1%，pCR 率为 20.3%。化疗相关毒性可耐受。
mFOLFOXIRI 新辅助化疗加选择性放疗似乎不会影响 LARC 的治疗效果。对于未经治疗的 LARC 患者，它可能是 CRT 的合理替代方案。
