对于局部晚期直肠癌，奥沙利铂加氟尿嘧啶为基础的术前化疗和术后化疗（德国CAO/ ARO/ AIO-04研究）：一项来自多中心、开放标签、随机的3期临床试验的最终结果背景德国CAO/ ARO/ AIO-94试验设立了术前滴注氟尿嘧啶化疗，全直肠系膜切除术，术后行氟尿嘧啶化疗作为局部晚期直肠癌一个标准的综合治疗模式。
在这里，我们比较先前的方案和一项研究性方案，在这项（研究性）方案中将奥沙利铂加入到了术前化疗和术后化疗中。
方法在这个多中心、开放标签、随机的3期研究中，我们将临床分期为cT3-4或淋巴结阳性的直肠腺癌患者随机分配为两组：一组接受标准氟尿嘧啶为基础的综合治疗模式，即术前放疗50.4Gy/28次加输注氟尿嘧啶（第1-5天、第29-33天，1000mg/m2），然后是手术和四个周期的氟尿嘧啶化疗（第1-5天和第29天，500mg/m2）；一组接受研究性方案，即术前放疗50.4Gy/28次加输注氟尿嘧啶（第1-14天、第22-35天，250mg/m2）和奥沙利铂（第1、8、22、29天，50mg/m2），然后是手术和八个周期奥沙利铂（第1、15天，100mg/m2）、亚叶酸（第1、15天，400mg/m2）和氟尿嘧啶（第1-2天、第15-16天，2400mg/m2）。
随机化是由计算机生成的数据块随机码完成的，按临床T分期（cT1-3 对比cT4）和临床N 分期（cN0对比cN1-2）进行分层。
主要终点是无病生存期，定义为随机化和非根治的原发肿瘤（R2切除）、R0 / 1切除之后局部复发、转移性疾病或恶化或任何原因的死亡之间的时间，不论哪个先出现。
生存率和复发累计发生率的分析在意向性治疗人群中完成；毒性分析包括所有治疗的患者。
患者在该试验的登记已完成，后续工作正在进行。
这项研究在上注册，注册号为NCT00349076。
发现最初入选了1265例患者，1236例可评估（研究组613例和对照组623例）。
中位随访50个月（IQR 38-61），3年无病生存率分别为：研究组75.9％（95％CI 72.4-79.5）和对照组71.2％（95％CI 67.6-74.9）（危险比[HR] 0.79，95％CI 0.64-0.98，P = 0.03）。
接受氟尿嘧啶和奥沙利铂的607例患者中有144例（24％）在化疗过程中发生术前3〜4级毒性作用，接受氟尿嘧啶化疗的625例患者中则有128例（20％）。
接受术后辅助氟尿嘧啶、亚叶酸钙和奥沙利铂的445例患者中有158例（36％）发生3-4级毒性作用，接受辅助氟尿嘧啶的470例患者中则有170例（36％）发生。
接受协议指定的术前和术后治疗的患者发生后期3〜4级不良事件，在研究组的445例中有112例（25％），在对照组的470例中100例（21％）。
解释与先前氟尿嘧啶为基础的综合治疗模式（基于CAO/ ARO/ AIO-94）相比，奥沙利铂加入氟尿嘧啶为基础的新辅助化疗和术后辅助化疗显著提高了临床分期为cT3-4或cN1-2直肠癌患者的无病生存率。
由CAO/ ARO/ AIO-04建立的方案可被视为治疗局部晚期直肠癌新的治疗选择。
桓兴医讯编译组田立霞2015年7月17日星期五ArticlesOxaliplatin added to fluorouracil-based preoperative chemoradiot herapy and postoperative chemotherapy of locally advanced rect al cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trialSummaryBackgroundPreoperative chemoradiotherapy with infusional fluorouracil, tot al mesorectal excision surgery, and postoperative chemotherapy with fluorouracil was established by the German CAO/ARO/AIO-94 trial as a standard combined modality treatment for local ly advanced rectal cancer. Here we compare the previously es tablished regimen with an investigational regimen in which ox aliplatin was added to both preoperative chemoradiotherapy and postoperative chemotherapy.MethodsIn this multicentre, open-label, randomised, phase 3 study we randomly assigned patients with rectal adenocarcinoma, clinic ally staged as cT3–4 or any node-positive disease, to two groups: a control group receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radioth erapy of 50·4Gy in 28 fractions plus infusional fluorourac il (1000 mg/m2 on days 1–5 and 29–33), followed by surger y and four cycles of bolus fluorouracil (500 mg/m2 on days 1–5 and 29); or to an investigational group receiving pre operative radiotherapy of 50·4Gy in 28 fractions plus infu sional fluorouracil (250 mg/m2 on days 1–14 and 22–35) and oxaliplatin (50 mg/m2 on days 1, 8, 22, and 29), followed by surgery and eight cycles of oxaliplatin (100 mg/m2 on days 1 and 15), leucovorin (400 mg/m2 on days 1 and 15), and infusional fluorouracil (2400 mg/m2on days 1–2 and 15–1 6). Randomisation was done with computer-generated block-random isation codes stratified by centre, clinical T category (cT1–3 vs cT4), and clinical N category (cN0 vs cN1–2) withou t masking. The primary endpoint was disease-free survival, de fined as the time between randomisation and non-radical surge ry of the primary tumour (R2 resection), locoregional recurre nce after R0/1 resection, metastatic disease or progression, or death from any cause, whichever occurred first. Survival and cumulative incidence of recurrence analyses followed theintention-to-treat principle; toxicity analyses included all pa tients treated. Enrolment of patients in this trial is compl eted and follow-up is ongoing. This study is registered with , number NCT00349076.FindingsOf the 1265 patients initially enrolled, 1236 were assessable (613 in the investigational group and 623 in the control group). With a median follow-up of 50 months (IQR 38–61), disease-free survival at 3 years was 75·9%(95% CI 72·4–7 9·5)in the investigational group and 71·2%(95% CI 67·6–74·9)in the control group (hazard ratio [HR] 0·79,95% CI 0·64–0·98;p=0·03).Preoperative grade 3–4 toxic eff ects occurred in 144 (24%) of 607 patients who actually rec eived fluorouracil and oxaliplatin during chemoradiotherapy and in 128 (20%) of 625 patients who actually received fluorou racil chemoradiotherapy. Of 445 patients who actually received adjuvant fluorouracil and leucovorin and oxaliplatin, 158 (3 6%) had grade 3–4 toxic effects, as did 170 (36%) of 470 patients who actually received adjuvant fluorouracil. Late g rade 3–4 adverse events in patients who received protocol-sp ecified preoperative and postoperative treatment occurred in 1 12 (25%) of 445 patients in the investigational group, and in 100 (21%) of 470 patients in the control group. InterpretationAdding oxaliplatin to fluorouracil-based neoadjuvant chemoradiot herapy and adjuvant chemotherapy (at the doses and intensitie s used in this trial) significantly improved disease-free sur vival of patients with clinically staged cT3–4 or cN1–2 re ctal cancer compared with our former fluorouracil-based combin ed modality regimen (based on CAO/ARO/AIO-94). The regimen es tablished by CAO/ARO/AIO-04 can be deemed a new treatment op tion for patients with locally advanced rectal cancer. FundingGerman Cancer Aid (Deutsche Krebshilfe).。