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背景和目的目前认为在食管癌、胃癌和直肠癌的治疗中,术前(新辅助)化疗和放疗相较于术后治疗更有效,这可能是由于术前治疗能更有效的减少微转移,并降低术中不完全切除及肿瘤细胞脱落的风险。FOxTROT研究旨在确定结肠癌患者术前化疗的可行性、安全性和有效性。方法本研究为准备进行的Ⅲ期随机对照研究的前期试验,研究共纳入150名影像学评估的局限进展期结肠癌(固有肌层浸润深度≥5 mm的T3期或T4期结肠癌)。患者来自英国35个中心,按2∶1随机分为术前化疗组和标准术后化疗组。术前化疗组治疗方案为OxMdG三个周期(奥沙利铂85 mg/m2,l-亚叶酸175 mg,氟尿嘧啶400 mg/m2推注,继之以2 400 mg/m2滴注46小时,术后追加9个疗程的OxMdG。标准术后化疗组为12个疗程的OxMdG。KRAS野生型患者按1∶1的比例接受或不接受帕尼单抗治疗(化疗前6周,每2周6 mg/kg方案)。通过中心随机化系统采用最小随机化方法对患者进行分组,分层因素包括年龄、影像学T和N分期、肿瘤部位以及是否结肠造口。本前期研究的主要终点为试验的可行性、安全性、患者对术前化疗的耐受性以及影像学分级方法的准确性。采用意向治疗分析法对研究结果进行分析。本研究通过伦理注册,编号ISRCTN 87163246。结果随机分组后,术前治疗组96%(95/99)的患者接受了术前化疗,其中89%(85/99)完成了全部疗程的治疗。7%(7/94)的患者出现3～ 4级胃肠道毒性反应。术前化疗组99名患者均成功完成肿瘤切除,并且与对照组相比,两组的术后并发症发生率无显著性差异。术前治疗组及对照组因术后并发症导致住院时间延长的比例分别为14%(14/99)和12%(5/51),P=0.81。术后病理证实为T3或以上的患者在术前治疗组和对照组的比例分别为91%(90/99)和98%(50/51),P=0.10。与对照组相比,术前化疗组显著降低TNM分期(P=0.04),包括2例病理完全缓解;淋巴结转移情况术前化疗组1%(1/98),对照组20%(10/50),P<0.0001;切缘阳性比例术前化疗组为4%(4/99),对照组为20%(10/50),P=0.002;盲法进行影像学评估肿瘤退缩术前化疗组为31%(29/94),对照组为2%(1/46),P=0.0001。结论通过影像学分期的局部进展期原发结肠癌患者行术前化疗可行。毒性反应和围手术期并发症发生率在可接受范围内。下一步有必要进行Ⅲ期临床试验以确定术前化疗组令人鼓舞的病理学反应能否改善长期预后。
BACKGROUND & OBJECTIVE It is currently considered that preoperative (neoadjuvant) chemotherapy and radiotherapy are more effective than postoperative treatment in the treatment of esophageal cancer, gastric cancer and rectal cancer, presumably because preoperative treatment is more effective in reducing micrometastases, And reduce the risk of incomplete resection and tumor cell shedding during surgery. The FOxTROT study was designed to determine the feasibility, safety and efficacy of preoperative chemotherapy in patients with colon cancer. METHODS: This was a prospective trial of phase III randomized controlled trials to be conducted in a cohort of 150 patients with locally advanced advanced colon cancers (stage T3 or T4 colon cancer with an intrinsic myometrial invasion ≥ 5 mm) enrolled. Patients from 35 centers in England were randomly divided into preoperative chemotherapy group and standard postoperative chemotherapy group according to 2: 1. The preoperative chemotherapy regimen consisted of OxMdG three cycles (oxaliplatin 85 mg / m2, l-leucovorin 175 mg, fluorouracil 400 mg / m2 bolus followed by 2,400 mg / m2 infusion for 46 hours Followed by an additional 9 courses of OxMdG. The standard postoperative chemotherapy group consisted of 12 courses of OxMdG.KRAS wild-type patients treated with or without panitumumab at a 1: 1 ratio (6 weeks prior to chemotherapy, 6 mg every 2 weeks / kg regimen) Patients were grouped by a minimal randomized approach using a central randomisation system that included age, radiographic T and N staging, tumor location, and colostomy.The primary endpoint of the current study was trial Feasibility, safety, patient tolerance to preoperative chemotherapy and the accuracy of imaging grading method.The research results were analyzed by intention-to-treat analysis.The research was ethically registered, number ISRCTN87163246.Results After randomization, Ninety-six percent (95/99) of the patients in the preoperative group received preoperative chemotherapy, of whom 89% (85/99) completed the full course of treatment.7% (7/94) of the patients developed grade 3-4 gastrointestinal Toxicology. Tumor resection was successfully performed in 99 patients in the preoperative chemotherapy group There was no significant difference in the incidence of postoperative complications between the two groups when compared with the control group, with 14% (14/99) and 12% (14/99) hospitalizations for preoperative and postoperative complications, respectively 5/51), P = 0.81. The proportion of preoperatively treated patients to control patients was 91% (90/99) and 98% (50/51), respectively Compared with the control group, preoperative chemotherapy significantly reduced the TNM stage (P = 0.04), including 2 cases of complete remission; lymph node metastasis in the preoperative chemotherapy group 1% (1/98), control group 20% (10 / 50), P <0.0001; positive margins of the margins were 4% (4/99) in the preoperative chemotherapy group and 20% (10/50) in the control group, P = 0.002; (29/94) in the control group and 2% (1/46) in the control group, P = 0.0001 .Conclusion The preoperative chemotherapy is feasible in patients with locally advanced primary colon cancer by imaging staging .Toxicity and perioperative The incidence of stage complications was within acceptable range.Next, there was a need for phase III clinical trials to determine whether the encouraging pathological response of the preoperative chemotherapy group improved long-term prognosis.