Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan.
Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
Jpn J Clin Oncol. 2022 Aug 5;52(8):850-858. doi: 10.1093/jjco/hyac080.
The optimal perioperative chemotherapy for lower rectal cancer with lateral pelvic lymph node metastasis remains unclear. We evaluated the efficacy and safety of perioperative mFOLFOX6 in comparison with postoperative mFOLFOX6 for rectal cancer patients undergoing total mesorectal excision with lateral lymph node dissection.
We conducted an open label randomized phase II/III trial in 18 Japanese institutions. We enrolled patients with histologically proven lower rectal adenocarcinoma with clinical pelvic lateral lymph node metastasis who were randomly assigned (1:1) to receive postoperative mFOLFOX6 (12 courses of intravenous oxaliplatin [85 mg/m2] with L-leucovorin [200 mg/m2] followed by 5-fluorouracil [400 mg/m2, bolus and 2400 mg/m2, continuous infusion, repeated every 2 weeks]) or perioperative mFOLFOX6 (six courses each preoperatively and postoperatively). The primary endpoint was overall survival (OS). The trial is registered with Japan Registry of Clinical Trials, number jRCTs031180230.
Between May 2015, and May 2019, 48 patients were randomized to the postoperative arm (n = 26) and the perioperative arm (n = 22). The trial was terminated prematurely due to poor accrual. The 3-year OS in the postoperative and perioperative groups were 66.1 and 84.4%, respectively (HR 0.58, 95% CI [0.14-2.45], one-sided P = 0.23). The pathological complete response rate in the perioperative group was 9.1%. Grade 3 postoperative surgical complications were more frequently observed in the perioperative arm (50.0 vs. 12.0%). One treatment-related death due to sepsis from pelvic infection occurred in the postoperative group.
Perioperative mFOLFOX6 may be an insufficient treatment to improve survival of lower rectal cancer with lateral pelvic lymph node metastasis.
对于伴有侧方盆腔淋巴结转移的低位直肠癌，最佳围手术期化疗方案仍不明确。我们评估了与术后 mFOLFOX6 相比，围手术期 mFOLFOX6 用于接受全直肠系膜切除术加侧方淋巴结清扫术的直肠癌患者的疗效和安全性。
我们在 18 家日本机构进行了一项开放标签的随机 II/III 期试验。我们纳入了经组织学证实的伴临床盆腔侧方淋巴结转移的低位直肠腺癌患者，将其随机（1:1）分配至术后 mFOLFOX6（12 个疗程的静脉注射奥沙利铂[85mg/m2]联合 L-左亚叶酸钙[200mg/m2]，随后给予氟尿嘧啶[400mg/m2，推注和 2400mg/m2，持续输注，每 2 周重复]）或围手术期 mFOLFOX6（术前和术后各 6 个疗程）治疗。主要终点为总生存期（OS）。该试验在日本临床试验注册处注册，编号为 jRCTs031180230。
2015 年 5 月至 2019 年 5 月，48 例患者被随机分至术后组（n=26）和围手术期组（n=22）。由于入组人数少，试验提前终止。术后组和围手术期组的 3 年 OS 分别为 66.1%和 84.4%（HR 0.58，95%CI [0.14-2.45]，单侧 P=0.23）。围手术期组的病理完全缓解率为 9.1%。围手术期组术后 3 级手术并发症更常见（50.0%比 12.0%）。术后组发生 1 例与治疗相关的脓毒症性盆腔感染死亡。
围手术期 mFOLFOX6 可能不足以改善伴有侧方盆腔淋巴结转移的低位直肠癌患者的生存。
