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
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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. / Al-Batran, Salah-Eddin; Homann, Nils; Pauligk, Claudia; Goetze, Thorsten O; Meiler, Johannes; Kasper, Stefan; Kopp, Hans-Georg; Mayer, Frank; Haag, Georg Martin; Luley, Kim; Lindig, Udo; Schmiegel, Wolff; Pohl, Michael; Stoehlmacher, Jan; Folprecht, Gunnar; Probst, Stephan; Prasnikar, Nicole; Fischbach, Wolfgang; Mahlberg, Rolf; Trojan, Jörg; Koenigsmann, Michael; Martens, Uwe M; Thuss-Patience, Peter; Egger, Matthias; Block, Andreas; Heinemann, Volker; Illerhaus, Gerald; Moehler, Markus; Schenk, Michael; Kullmann, Frank; Behringer, Dirk M; Heike, Michael; Pink, Daniel; Teschendorf, Christian; Löhr, Carmen; Bernhard, Helga; Schuch, Gunter; Rethwisch, Volker; von Weikersthal, Ludwig Fischer; Hartmann, Jörg T; Kneba, Michael; Daum, Severin; Schulmann, Karsten; Weniger, Jörg; Belle, Sebastian; Gaiser, Timo; Oduncu, Fuat S; Güntner, Martina; Hozaeel, Wael; Reichart, Alexander; Jäger, Elke; Kraus, Thomas; Mönig, Stefan; Bechstein, Wolf O; Schuler, Martin; Schmalenberg, Harald; Hofheinz, Ralf D; FLOT4-AIO Investigators.
in: LANCET, Jahrgang 393, Nr. 10184, 11.05.2019, S. 1948-1957.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - 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
AU - Al-Batran, Salah-Eddin
AU - Homann, Nils
AU - Pauligk, Claudia
AU - Goetze, Thorsten O
AU - Meiler, Johannes
AU - Kasper, Stefan
AU - Kopp, Hans-Georg
AU - Mayer, Frank
AU - Haag, Georg Martin
AU - Luley, Kim
AU - Lindig, Udo
AU - Schmiegel, Wolff
AU - Pohl, Michael
AU - Stoehlmacher, Jan
AU - Folprecht, Gunnar
AU - Probst, Stephan
AU - Prasnikar, Nicole
AU - Fischbach, Wolfgang
AU - Mahlberg, Rolf
AU - Trojan, Jörg
AU - Koenigsmann, Michael
AU - Martens, Uwe M
AU - Thuss-Patience, Peter
AU - Egger, Matthias
AU - Block, Andreas
AU - Heinemann, Volker
AU - Illerhaus, Gerald
AU - Moehler, Markus
AU - Schenk, Michael
AU - Kullmann, Frank
AU - Behringer, Dirk M
AU - Heike, Michael
AU - Pink, Daniel
AU - Teschendorf, Christian
AU - Löhr, Carmen
AU - Bernhard, Helga
AU - Schuch, Gunter
AU - Rethwisch, Volker
AU - von Weikersthal, Ludwig Fischer
AU - Hartmann, Jörg T
AU - Kneba, Michael
AU - Daum, Severin
AU - Schulmann, Karsten
AU - Weniger, Jörg
AU - Belle, Sebastian
AU - Gaiser, Timo
AU - Oduncu, Fuat S
AU - Güntner, Martina
AU - Hozaeel, Wael
AU - Reichart, Alexander
AU - Jäger, Elke
AU - Kraus, Thomas
AU - Mönig, Stefan
AU - Bechstein, Wolf O
AU - Schuler, Martin
AU - Schmalenberg, Harald
AU - Hofheinz, Ralf D
AU - FLOT4-AIO Investigators
N1 - Copyright © 2019 Elsevier Ltd. All rights reserved.
PY - 2019/5/11
Y1 - 2019/5/11
N2 - 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/m2 epirubicin and 60 mg/m2 cisplatin on day 1 plus either 200 mg/m2 fluorouracil as continuous intravenous infusion or 1250 mg/m2 capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin and 2600 mg/m2 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.FUNDING: The German Cancer Aid (Deutsche Krebshilfe), Sanofi-Aventis, Chugai, and Stiftung Leben mit Krebs Foundation.
AB - 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/m2 epirubicin and 60 mg/m2 cisplatin on day 1 plus either 200 mg/m2 fluorouracil as continuous intravenous infusion or 1250 mg/m2 capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin and 2600 mg/m2 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.FUNDING: The German Cancer Aid (Deutsche Krebshilfe), Sanofi-Aventis, Chugai, and Stiftung Leben mit Krebs Foundation.
KW - Adenocarcinoma/drug therapy
KW - Administration, Oral
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antineoplastic Combined Chemotherapy Protocols/administration & dosage
KW - Capecitabine/administration & dosage
KW - Cisplatin/administration & dosage
KW - Digestive System Surgical Procedures
KW - Disease-Free Survival
KW - Docetaxel/administration & dosage
KW - Esophagogastric Junction/pathology
KW - Female
KW - Fluorouracil/administration & dosage
KW - Humans
KW - Leucovorin/administration & dosage
KW - Male
KW - Middle Aged
KW - Neoplasm Staging
KW - Oxaliplatin/administration & dosage
KW - Stomach Neoplasms/drug therapy
KW - Treatment Outcome
U2 - 10.1016/S0140-6736(18)32557-1
DO - 10.1016/S0140-6736(18)32557-1
M3 - SCORING: Journal article
C2 - 30982686
VL - 393
SP - 1948
EP - 1957
JO - LANCET
JF - LANCET
SN - 0140-6736
IS - 10184
ER -