Institute of Clinical Cancer Research, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt, Germany; IKF Klinische Krebsforschung GmbH am Krankenhaus Nordwest, Frankfurt, Germany.
Klinikum Wolfsburg, Wolfsburg, Germany.
Lancet. 2019 May 11;393(10184):1948-1957. doi: 10.1016/S0140-6736(18)32557-1. Epub 2019 Apr 11.
Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma. This study reports on the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) as a perioperative therapy for patients with locally advanced, resectable tumours.
In this controlled, open-label, phase 2/3 trial, we randomly assigned 716 patients with histologically-confirmed advanced clinical stage cT2 or higher or nodal positive stage (cN+), or both, resectable tumours, with no evidence of distant metastases, via central interactive web-based-response system, to receive either three pre-operative and three postoperative 3-week cycles of 50 mg/m epirubicin and 60 mg/m cisplatin on day 1 plus either 200 mg/m fluorouracil as continuous intravenous infusion or 1250 mg/m capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m docetaxel, 85 mg/m oxaliplatin, 200 mg/m leucovorin and 2600 mg/m fluorouracil as 24-h infusion on day 1 (FLOT; experimental group). The primary outcome of the trial was overall survival (superiority) analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01216644.
Between Aug 8, 2010, and Feb 10, 2015, 716 patients were randomly assigned to treatment in 38 German hospitals or with practice-based oncologists. 360 patients were assigned to ECF/ECX and 356 patients to FLOT. Overall survival was increased in the FLOT group compared with the ECF/ECX group (hazard ratio [HR] 0·77; 95% confidence interval [CI; 0.63 to 0·94]; median overall survival, 50 months [38·33 to not reached] vs 35 months [27·35 to 46·26]). The number of patients with related serious adverse events (including those occurring during hospital stay for surgery) was similar in the two groups (96 [27%] in the ECF/ECX group vs 97 [27%] in the FLOT group), as was the number of toxic deaths (two [<1%] in both groups). Hospitalisation for toxicity occurred in 94 patients (26%) in the ECF/ECX group and 89 patients (25%) in the FLOT group.
In locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, perioperative FLOT improved overall survival compared with perioperative ECF/ECX.
The German Cancer Aid (Deutsche Krebshilfe), Sanofi-Aventis, Chugai, and Stiftung Leben mit Krebs Foundation.
多西紫杉醇为基础的化疗对转移性胃和胃食管交界处腺癌有效。本研究报告了基于多西紫杉醇的三联 FLOT（氟尿嘧啶加亚叶酸、奥沙利铂和多西紫杉醇）作为局部晚期可切除肿瘤患者围手术期治疗的安全性和有效性。
在这项对照、开放标签、2/3 期试验中，我们通过中央交互式网络响应系统随机分配 716 名组织学证实为临床晚期 cT2 或更高或淋巴结阳性（cN+）或两者均有、可切除肿瘤且无远处转移证据的患者，通过中央交互式网络响应系统接受三种术前和三种术后 3 周周期的 50mg/m 表柔比星和 60mg/m 顺铂，第 1 天加 200mg/m 氟尿嘧啶持续静脉输注或 1250mg/m 卡培他滨口服，第 1 至 21 天（ECF/ECX；对照组）或术前和术后四个 2 周周期的 50mg/m 多西紫杉醇、85mg/m 奥沙利铂、200mg/m 亚叶酸和 2600mg/m 氟尿嘧啶作为 24 小时输注，第 1 天（FLOT；实验组）。试验的主要终点是总生存（优势），在意向治疗人群中进行分析。该试验在 ClinicalTrials.gov 上注册，编号为 NCT01216644。
2010 年 8 月 8 日至 2015 年 2 月 10 日，716 名患者被随机分配到德国 38 家医院或基于实践的肿瘤学家的治疗中。360 名患者被分配到 ECF/ECX 组，356 名患者被分配到 FLOT 组。与 ECF/ECX 组相比，FLOT 组的总生存率增加（风险比[HR]0.77；95%置信区间[CI；0.63 至 0.94]；中位总生存率，50 个月[38.33 至未达到]与 35 个月[27.35 至 46.26]）。两组发生相关严重不良事件（包括手术期间住院期间发生的事件）的患者数量相似（ECF/ECX 组 96 [27%]，FLOT 组 97 [27%]），毒性死亡人数也相似（两组均为 2 [<1%]）。ECF/ECX 组有 94 名（26%）患者因毒性住院，FLOT 组有 89 名（25%）患者因毒性住院。
在局部晚期可切除的胃或胃食管交界处腺癌中，围手术期 FLOT 可提高总生存率，而不是围手术期 ECF/ECX。
德国癌症援助协会（Deutsche Krebshilfe）、赛诺菲-安万特、中外制药和癌症生活基金会。
