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
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
- Department of internal Medicine I
- University Cancer Center Frankfurt (UCT)
- Wolfsburg Hospital
- University of Duisburg-Essen
- Robert Bosch Centrum für Tumorerkrankungen (RBCT)
- University Hospital Tübingen
- Universitätsklinikum Schleswig-Holstein - Campus Lübeck
- Jena University Hospital
- Ruhr University Bochum
- University Hospital Carl Gustav Carus Dresden
- Central Hospital Bielefeld
- Asklepios Hospital Hamburg-Barmbek
- Klinikum Aschaffenburg-Alzenau
- Klinikum Mutterhaus der Borromäerinnen gGmbH
- University Hospital Frankfurt
- MediProjekt
- SLK-Kliniken Heilbronn GmbH
- Charité – Universitätsmedizin Berlin
- Ortenau Klinikum Lahr
- University Hospital Hamburg Eppendorf
- Klinikum Stuttgart
- Johannes Gutenberg University Mainz
- Hospital of the Brothers of Mercy Regensburg
- Kliniken Nordoberpfalz – Klinikum Weiden
- Augusta Hospitals Bochum Hattingen
- Municipal Hospital Dortmund
- Helios Hospital Group
- St.-Josefs-Hospital Dortmund
- Helios HSK Clincs Wiesbaden
- Darmstadt Clinics
- Hämatologisch-Onkologische Praxis Altona (HOPA)
- Hämatologisch-Onkologische Praxis Eppendorf (HOPE)
- Franziskus Hospital Bielefeld
- University Hospital Schleswig-Holstein Campus Kiel
- MVZ Arnsberg
- Gemeinschaftspraxis Dr. Weniger /Dr. Bittrich/Dr. Schütze
- Leibniz University Hannover (LUH)
- Trium Analysis Online GmbH
- Am Marienhospital
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.
Details
Original language | English |
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Pages (from-to) | 1948-1957 |
Number of pages | 10 |
Journal | The Lancet |
Volume | 393 |
Issue number | 10184 |
Publication status | Published - 11 May 2019 |
Peer-reviewed | Yes |
External IDs
Scopus | 85064895961 |
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ORCID | /0000-0002-9321-9911/work/142251969 |
Keywords
Sustainable Development Goals
Keywords
- Adenocarcinoma/drug therapy, Administration, Oral, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Capecitabine/administration & dosage, Cisplatin/administration & dosage, Digestive System Surgical Procedures, Disease-Free Survival, Docetaxel/administration & dosage, Esophagogastric Junction/pathology, Female, Fluorouracil/administration & dosage, Humans, Leucovorin/administration & dosage, Male, Middle Aged, Neoplasm Staging, Oxaliplatin/administration & dosage, Stomach Neoplasms/drug therapy, Treatment Outcome