Kagawa Yoshinori, Ando Koji, Uemura Mamoru, Watanabe Jun, Oba Koji, Emi Yasunori, Matsuhashi Nobuhisa, Izawa Naoki, Muto Osamu, Kinjo Tatsuya, Takemasa Ichiro, Oki Eiji
Department of Gastroenterological Surgery Osaka General Medical Center Osaka Japan.
Department of Gastroenterological Surgery Osaka International Cancer Institute Osaka Japan.
Ann Gastroenterol Surg. 2024 Aug 3;8(6):1067-1075. doi: 10.1002/ags3.12848. eCollection 2024 Nov.
To evaluate the feasibility and safety of total neoadjuvant therapy with long-course chemoradiotherapy followed by consolidation chemotherapy in Japanese patients with locally advanced rectal cancer.
This prospective, multicenter, single-arm, phase II trial was conducted at 10 centers. The eligibility criteria included age ≥20 y, locally advanced rectal cancer within 12 cm of the anal verge, and cT3-4N0M or TanyN+M0 at diagnosis, enabling curative resection. The protocol treatment was capecitabine (1650 mg/m/day)-based long-course chemoradiotherapy (50.4 Gy/28 fractions) and consolidation chemotherapy (CAPOX, four courses) followed by total mesorectal excision. Nonoperative management was allowed if a clinical complete response was achieved. The primary endpoint was the pathologic complete response rate.
Among 28 enrolled patients (19 men, 9 women; median age, 69.5 [41-79] y), the long-course chemoradiotherapy and consolidation chemotherapy completion rates were 100% and 96.4%, respectively. The clinical responses included clinical complete response, (35.7%, 10/28), near-complete response (28.6%, 8/28), and incomplete response (32.1%, 9/28). Total mesorectal excision and nonoperative management were performed in 21 and six patients, respectively. The final analysis included 21 patients. Five patients (23.8% [90% confidence interval 11.8%-41.8%]) achieved pathologic complete response, while 10 of 28 patients (35.7%) achieved a pathological complete response or a sustained clinical complete response. No treatment-related deaths occurred. Grade ≥3 adverse events included diarrhea (7.1%) and leukopenia (7.1%).
ENSEMBLE-2 demonstrated comparable pathologic complete response rates and well-tolerated safety of total neoadjuvant therapy with long-course chemoradiotherapy followed by consolidation chemotherapy in Japanese patients with locally advanced rectal cancer.
评估长程放化疗联合巩固化疗的全新辅助治疗方案在日本局部晚期直肠癌患者中的可行性和安全性。
本前瞻性、多中心、单臂II期试验在10个中心开展。纳入标准包括年龄≥20岁、距肛缘12 cm以内的局部晚期直肠癌、诊断时为cT3-4N0M0或TanyN+M0且可行根治性切除。方案治疗为基于卡培他滨（1650 mg/m²/天）的长程放化疗（50.4 Gy/28次分割）和巩固化疗（CAPOX方案，4个疗程），随后行全直肠系膜切除术。若达到临床完全缓解，则允许非手术治疗。主要终点为病理完全缓解率。
在28例入组患者（19例男性，9例女性；中位年龄69.5[41 - 79]岁）中，长程放化疗和巩固化疗的完成率分别为100%和96.4%。临床反应包括临床完全缓解（35.7%，10/28）、接近完全缓解（28.6%，8/28）和部分缓解（32.1%，9/28）。分别有21例和6例患者接受了全直肠系膜切除术和非手术治疗。最终分析纳入21例患者。5例患者（23.8%[90%置信区间11.8% - 41.8%]）达到病理完全缓解，而28例患者中有10例（35.7%）达到病理完全缓解或持续临床完全缓解。未发生与治疗相关的死亡。≥3级不良事件包括腹泻（7.1%）和白细胞减少（7.1%）。
ENSEMBLE-2研究表明，在日本局部晚期直肠癌患者中，长程放化疗联合巩固化疗的全新辅助治疗方案具有相当的病理完全缓解率且安全性良好，耐受性佳。
