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

FLOT4-AIO Investigators

doi:10.1016/S0140-6736(18)32557-1

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

FLOT4-AIO Investigators

Abstract

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.

Original language	English
Journal	The Lancet
Volume	393
Issue number	10184
Pages (from-to)	1948-1957
Number of pages	10
ISSN	0140-6736
DOIs	https://doi.org/10.1016/S0140-6736(18)32557-1
Publication status	Published - 11.05.2019

Funding

S-EA-B has an advisory role with Merck, Roche, Celgene, Lilly, Nordic Pharma, Bristol-Myers Squibb and MSD Sharp & Dohme; is a speaker for Roche, Celgene, Lilly, Nordic Pharma, AIO gGmbH, MCI, promedicis, and Forum für Medizinische Fortbildung; he is CEO/founder of IKF Klinische Krebsforschung GmbH; and has received research grants from Sanofi, Merck, Roche, Celgene, Vifor, Medac, Hospira, Lilly, Bristol-Myers Squibb, German Cancer Aid (Krebshilfe), German Research Foundation, and the Federal Ministry of Education and Research. MS is a consultant to AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, and Roche; has received honoraries for CME presentations with Abbvie, Alexion, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, MSD, Novartis, and Pierre Fabre; his institution has received research funding from Boehringer Ingelheim, Bristol-Myers Squibb, and Novartis; and he holds patents with Universität Duisburg-Essen. None of the above is related to or has influenced the work presented here. HS has an advisory role for BMS, Lilly, and Novartis and has received research grants from Sanofi. CT is a speaker for Roche. TOG has an advisory role with Lilly, MSD Sharp & Dohme, Shire, Bayer, Celgene, and Servier; is a speaker for Lilly, MCI, MSD Sharp & Dohme; and has received research grants from German Research Foundation. KS has an advisory role with Amgen, Bristol-Myers Squibb, Merck, Novartis, and Roche; is a speaker for Roche; and has received travel support and congress fee compensation from Abbvie, Bristol-Myers Squibb, Celgene, and Lilly. GMH reports fees for advisory role from BMS, Taiho, Nordic, Lilly, and MSD; honoraria from Roche and Pfizer, travel grants from Amgen, Ipsen, Celgene, and BMS; research funding is provided by Nordic and Taiho Pharmaceuticals. JM is a consultant to Roche, Bristol-Myers Squibb, and Sanofi-Aventis Lilly and reports personal fees from Amgen. SK is a consultant to AstraZeneca, Amgen, Bristol-Myers Squibb, Lilly, Merck, MSD Sharp & Dohme, Sanofi-Aventis, Servier, Shire, and Roche; received Honoraries for CME presentations from AstraZeneca, Amgen, Bristol-Myers Squibb, Lilly, Merck, MSD Sharp & Dohme, Roche, Sanofi-Aventis, Servier, and Shire. His institution received research funding from Bristol Myers-Squibb, Celgene, Lilly, Merck, Roche and Servier. SD had an advisory role with Amgen and has an advisory role with Bristol-Myers Squibb and is a speaker for Sanofi, Recordati, Amgen and Falk. MP reports personal fees from Roche Pharma AG, Amgen AG, MSD Sharp & Dohme GMBH, MCI Deutschland GmbH, Merck Serono, Sanofi Aventis, BMS, Baxalta-Shire, Chugai, Celgene, Roche Pharma AG, Servier, Dres-Schlegel + Schmidt, and Lilly; and is a consultant in haematology and oncology and an employee of Universitätsklinikum Knappschaftskrankenhaus Bochum, Ruhr university bochum. WS reports grants from German Cancer Aid, during the conduct of the study; personal fees from AiCuris, Amgen, Apceth, Indivumed, Merck Serono, 4SC, Deutschlandfunk (DLF Deutsches Ärzteblatt, Elsevier Verlag, Springer Verlag, Westdeutscher Rundfunk (WDR), personal fees from Zweites Deutsches Fernsehen (ZDF), Falk Foundation, Lilly Deutschland GmbH, MCI, Pfizer, Roche, Sanofi, Aventis, Siemens Healthcare, Dres-Schlegel + Schmidt, Deutscher Ärzteverlag, Labor Berlin-Charité Vivantes Services GmbH, and Servier Deutschland; grants from Sysmex Deutschland GmbH - Research Corporation, investigator staff honoraria from Ganymed, other from Celgene, other from Hoffmann La Roche, outside the submitted work. DP has an advisory role with Roche, Lilly, PharmaMar, and Clinigen; is a speaker for Lilly and PharmaMar and has received research grants from Lilly, PharmaMar, Novartis, and Clinigen. PT-P has an advisory role with Roche, MSD Sharp & Dohme, Bristol-Myers Squibb, Merck, and Nordic, and had travel expenses covered by Roche, Merck, and Lilly, outside the submitted work. JT reports personal fees from Amgen, Bayer Healthcare, Bioprojet, Bristol-Myers Squibb, Celgene, Daichi Sankyo, Ipsen, Imclone, Roche, Servier, and Shire, outside the submitted work. MM has compensated consultant or advisory relationships with Falk foundation, Nordic, Amgen, AstraZeneca, MCI, Lilly, MSD, MerckSerono, Pfizer, BMS, Onyx, and Roche and received research grants by Amgen, BMS, MSD, MerckSerono, Taiho, Roche, AIO gGmbH, and EORTC. UMM has an advisory role with Merck, Roche, Celgene, Lilly, Bristol-Myers Squibb, Sanofi, and MSD Sharp & Dohme. NH has an advisory role with Sanofi, Roche, Amgen, Lilly, Servier, and Bristol-Myers Squibb and is a speaker for Sanofi, Roche, Amgen, Merck, Celgene, MSD Sharp & Dohme, and Servier. VH reports honoraria from Merck, Roche, Celgene, AMGEN, Sanofi, Lilly, SIRTEX, Boehringer Ingelheim, Taiho, and Servier; consulting or advisory board activities for Merck, Roche, AMGEN, Sanofi, SIRTEX, Servier, Celgene, Boehringer Ingelheim, Halozyme, MSD, and BMS; research funding from MERCK, Roche, AMGEN, SIRTEX, Servier, Celgene, Boehringer-Ingelheim, and Shire and travel accommodation expenses from MERCK, Roche, AMGEN, SIRTEX, Servier, Shire, MSD, and BMS. WOB has served on an advisory board for Astellas and has received honoraria and travel reimbursement from Astellas, Baxter, Integra, MCI Deutschland, Medupdate GmbH, MerckSerono, and TEVA. DMB has an advisory role with Boehringer Ingelheim, Bristol-Myers Squibb, and Roche. GF has received a research grant from Merck-Serono and has received honoraries from Merck-Serono, Roche/Genentech, Sanofi-Aventis, Bristol-Myers Squibb, Merck Sharp Dome, Servier, Lilly, Amgen, Mundipharma, and Shire. RDH has an advisory role with Merck, Roche, Boehringer Ingelheim, Sanofi-Aventis, Lilly, Bristol-Myers Squibb, and MSD Sharp & Dohme; is a speaker for Roche, Merck, Lilly, Sanofi-Aventis, Bristol-Myers Squibb, and MSD Sharp & Dohme and has received research grants from Amgen, Sanofi, Merck, Roche, medac, and German Cancer Aid (Krebshilfe). H-GK reports personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Pierre Fabre, Roche, personal fees from PharmaMar, and Pfizer, outside the submitted work. WF reports personal fees from Abbot, AbbieVie Deutschland, Bio Merieux, Boehringer Ingelheim, Falk, Kibion, Norgine, Pfizer, and Reckitt Benckiser, outside the submitted work. RM reports non-financial support from Amgen, Merck, and Novartis, outside the submitted work. GS has an advisory role with Novartis and Sanofi-Aventis. All other authors declare no competing interests.

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Dive into the research topics of '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'. Together they form a unique fingerprint.

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FLOT4-AIO Investigators (2019). 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. The Lancet, 393(10184), 1948-1957. https://doi.org/10.1016/S0140-6736(18)32557-1

@article{c287afd5acbf4e7cacb3c7759933ac63,

title = "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",

abstract = "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.",

author = "\{FLOT4-AIO Investigators\} and Al-Batran, \{Salah Eddin\} and Nils Homann and Claudia Pauligk and Goetze, \{Thorsten O.\} and Johannes Meiler and Stefan Kasper and Kopp, \{Hans Georg\} and Frank Mayer and Haag, \{Georg Martin\} and Kim Luley and Udo Lindig and Wolff Schmiegel and Michael Pohl and Jan Stoehlmacher and Gunnar Folprecht and Stephan Probst and Nicole Prasnikar and Wolfgang Fischbach and Rolf Mahlberg and J{\"o}rg Trojan and Michael Koenigsmann and Martens, \{Uwe M.\} and Peter Thuss-Patience and Matthias Egger and Andreas Block and Volker Heinemann and Gerald Illerhaus and Markus Moehler and Michael Schenk and Frank Kullmann and Behringer, \{Dirk M.\} and Michael Heike and Daniel Pink and Christian Teschendorf and Carmen L{\"o}hr and Helga Bernhard and Gunter Schuch and Volker Rethwisch and \{von Weikersthal\}, \{Ludwig Fischer\} and Hartmann, \{J{\"o}rg T.\} and Michael Kneba and Severin Daum and Karsten Schulmann and J{\"o}rg Weniger and Sebastian Belle and Timo Gaiser and Oduncu, \{Fuat S.\} and Martina G{\"u}ntner and Wael Hozaeel and Alexander Reichart",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2019",

month = may,

day = "11",

doi = "10.1016/S0140-6736(18)32557-1",

language = "English",

volume = "393",

pages = "1948--1957",

journal = "The Lancet",

issn = "0140-6736",

publisher = "Elsevier B.V.",

number = "10184",

}

FLOT4-AIO Investigators 2019, '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', The Lancet, vol. 393, no. 10184, pp. 1948-1957. https://doi.org/10.1016/S0140-6736(18)32557-1

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. / FLOT4-AIO Investigators.
In: The Lancet, Vol. 393, No. 10184, 11.05.2019, p. 1948-1957.

Research output: Journal Articles › Journal articles › Research › peer-review

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 - FLOT4-AIO Investigators

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

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.

UR - https://www.scopus.com/pages/publications/85064895961

U2 - 10.1016/S0140-6736(18)32557-1

DO - 10.1016/S0140-6736(18)32557-1

M3 - Journal articles

C2 - 30982686

AN - SCOPUS:85064895961

SN - 0140-6736

VL - 393

SP - 1948

EP - 1957

JO - The Lancet

JF - The Lancet

IS - 10184

ER -

FLOT4-AIO Investigators. 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. The Lancet. 2019 May 11;393(10184):1948-1957. doi: 10.1016/S0140-6736(18)32557-1

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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