Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial

被引：1722

作者：

Al-Batran, Salah-Eddin ^{[1
,2
]}

Homann, Nils ^{[3
]}

Pauligk, Claudia ^{[1
,2
]}

Goetze, Thorsten O. ^{[1
,2
]}

Meiler, Johannes ^{[4
]}

Kasper, Stefan ^{[4
]}

Kopp, Hans-Georg ^{[6
]}

Mayer, Frank ^{[7
]}

Haag, Georg Martin ^{[8
]}

Luley, Kim ^{[9
]}

Lindig, Udo ^{[10
]}

Schmiegel, Wolff ^{[11
,12
]}

Pohl, Michael ^{[11
]}

Stoehlmacher, Jan ^{[13
]}

Folprecht, Gunnar ^{[13
]}

Probst, Stephan ^{[14
]}

Prasnikar, Nicole ^{[15
]}

Fischbach, Wolfgang ^{[16
]}

Mahlberg, Rolf ^{[17
]}

Trojan, Joerg ^{[18
]}

Koenigsmann, Michael ^{[19
]}

Martens, Uwe M. ^{[20
]}

Thuss-Patience, Peter ^{[21
]}

Egger, Matthias ^{[23
]}

Block, Andreas ^{[24
]}

Heinemann, Volker ^{[25
]}

Illerhaus, Gerald ^{[26
]}

Moehler, Markus ^{[27
]}

Schenk, Michael ^{[28
]}

Kullmann, Frank ^{[29
]}

Behringer, Dirk M. ^{[30
]}

Heike, Michael ^{[31
]}

Pink, Daniel ^{[32
,33
]}

Teschendorf, Christian ^{[34
]}

Loehr, Carmen ^{[35
]}

Bernhard, Helga ^{[36
]}

Schuch, Gunter ^{[37
]}

Rethwisch, Volker ^{[38
]}

von Weikersthal, Ludwig Fischer ^{[39
]}

Hartmann, Joerg T. ^{[40
]}

Kneba, Michael ^{[41
]}

Daum, Severin ^{[22
]}

Schulmann, Karsten ^{[42
]}

Weniger, Joerg

Belle, Sebastian ^{[43
]}

Gaiser, Timo ^{[44
]}

Oduncu, Fuat S. ^{[45
]}

Guentner, Martina ^{[46
]}

Hozaeel, Wael ^{[47
]}

Reichart, Alexander ^{[48
]}

机构：

[1] Krankenhaus NW Frankfurt, UCT Univ Canc Ctr, Inst Clin Canc Res, D-60488 Frankfurt, Germany

[2] Krankenhaus NW Frankfurt, IKF Klin Krebsforsch GmbH, Frankfurt, Germany

[3] Klinikum Wolfsburg, Wolfsburg, Germany

[4] Univ Duisburg Essen, Dept Med Oncol, West German Canc Ctr, Essen, Germany

[5] Partner Site Univ Hosp Essen, German Canc Consortium DKTK, Essen, Germany

[6] RBCT, Stuttgart, Germany

[7] Univ Klinikum Eberhard Karls Univ, Med Klin 2, Abt Onkol Hamatol Immunol Rheumatol Pneumol, Tubingen, Germany

[8] Univ Klinikum Heidelberg, Natl Ctr Tumorerkrankungen, Abt Med Onkol, Heidelberg, Germany

[9] Univ Klinikum Schleswig Holstein, Klin Hamatol & Onkol, Lubeck, Germany

[10] Univ Klinikum Jena, Klin Innere Med 2, Abt Hamatol & Onkol, Jena, Germany

[11] Ruhr Univ Bochum, Dept Med, Univ Klinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Germany

[12] Ruhr Univ Bochum, Berufsgenossenschaftliches Univ Klinikum Bergmann, Dept Gastroenterol & Hepatol, Bochum, Germany

[13] Univ Klinikum Carl Gustav Carus, Med Klin & Poliklin 1, Dresden, Germany

[14] Klinikum Bielefeld, Klin Hamatol & Onkol, Bielefeld, Germany

[15] Asklepios Klin Barmbek, Hamatol Onkol & Palliat Med, Hamburg, Germany

[16] Klinikum Aschaffenburg, Med Klin 2, Gastroenterol & Onkol, Aschaffenburg, Germany

[17] Klinikum Mutterhaus Borromaerinnen, Med Klin 1, Trier, Germany

[18] Goethe Univ, Univ Klinikum Frankfurt, Med Klin 1, Frankfurt, Germany

[19] Gesell Med Stat & Projektentwicklung, MediProjekt, Hannover, Germany

[20] SLK Kliniken GmbH, Canc Ctr Heilbronn Franken, Klin Innere Med 3, Heilbronn, Germany

[21] Charite Univ Med Berlin, Med Klin S Hamatol Onkol & Tumorimmunol, Berlin, Germany

[22] Charite Univ Med Berlin, Klin Gastroenterol Infektiol & Rheumatol, Berlin, Germany

[23] Ortenau Klinikum Lahr, Med Klin, Gastroenterol & Onkol, Sekt Hamatol & Onkol, Lahr, Germany

[24] Univ Klinikum Hamburg Eppendorf, Med Klin & Poliklin Onkol Hamatol 2, UCCH, KMT,Sekt Pneumol, Hamburg, Germany

[25] Klinikum Univ Munchen, Med Klin & Poliklin 3, Campus Grosshadern, Munich, Germany

[26] Klinikum Stuttgart, Klin Hamatol Onkol & Palliat Med, Stuttgart, Germany

[27] Johannes Gutenberg Univ Mainz, Med Klin & Poliklin 1, Mainz, Germany

[28] Krankenhaus Barmherzige Bruder Regensburg, Klin Onkol & Hamatol, Regensburg, Germany

[29] Klinikum Weiden, Med Klin 1, Weiden, Germany

[30] Augusta Krankenanstalt Bochum, Klin Hamatol & Onkol, Bochum, Germany

[31] Klinikum Dortmund gGmbH, Med Klin, Gastroenterol Hamatol Onkol Endokrinol, Dortmund, Germany

[32] Helios Klinikum Bad Saarow, Klin Hamatol Onkol & Palliat Med, Bad Saarow Pieskow, Germany

[33] Univ Med Greifswald, Klin & Poliklin Innere Med C, Hamatol & Onkol & Transplantat Zentrum, Greifswald, Germany

[34] St Josefs Hosp, Innere Med Klin, Dortmund, Germany

[35] Horst Schmidt Kliniken, Innere Med 2, Wiesbaden, Germany

[36] Klinikum Darmstadt, Med Klin 5, Hamatol & Onkol, Darmstadt, Germany

[37] HOPA, Hamburg, Germany

[38] Klinikum Dortmund gGmbH, Med Klin, Gastroenterol Hamatol Onkol Endokrinol, Dortmund, Germany

[39] MVZ Gesundheitszentrum St Marien GmbH, Hamatol Internist Onkol, Amberg, Germany

[40] Franziskus Hosp Bielefeld, Catholic Hosp Consortium Eastern Westphalia, Klin Innere Med Hamatol Internist Onkol Immunol 2, Bielefeld, Germany

[41] Univ Clin Schleswig Holstein, Klin Innere Med Hamatol & Onkol 2, Campus Kiel, Kiel, Germany

[42] MVZ Arnsberg, Praxis Hamatol & Onkol, Arnsberg, Germany

[43] Univ Med Mannheim, Med Klin 2, Mannheim, Germany

[44] Univ Med Mannheim, Inst Pathol, Mannheim, Germany

[45] Klinikum Univ Munchen, Med Klin & Poliklin 3, Munich, Germany

[46] Trium Anal Online, Munich, Germany

[47] Marienhospital, MVZ Onkol GmbH, Hagen, Germany

[48] Krankenhaus NW Frankfurt, UCT Univ Canc Ctr, Klin Onkol & Hamatol, Frankfurt, Germany

[49] Krankenhaus NW Frankfurt, UCT Univ Canc Ctr, Klin Allgemein Viszeral & Minimal Invas Chirurg, Frankfurt, Germany

[50] Hop Univ Geneve, Serv Chirurg Viscerale, Geneva, Switzerland

来源：

LANCET | 2019年 / 393卷 / 10184期

关键词：

OPEN-LABEL; CANCER; MULTICENTER; CHEMORADIOTHERAPY; RESECTION; SURGERY; ESOPHAGEAL; REGRESSION; STOMACH;

D O I：

10.1016/S0140-6736(18)32557-1

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background 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. Methods 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(2) epirubicin and 60 mg/m(2) cisplatin on day 1 plus either 200 mg/m(2) fluorouracil as continuous intravenous infusion or 1250 mg/m(2) capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m(2) docetaxel, 85 mg/m(2) oxaliplatin, 200 mg/m(2) leucovorin and 2600 mg/m(2) 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. Findings 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. Interpretation In locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, perioperative FLOT improved overall survival compared with perioperative ECF/ECX. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

引用

页码：1948 / 1957

页数：10

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