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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.
- Source :
-
Lancet (London, England) [Lancet] 2019 May 11; Vol. 393 (10184), pp. 1948-1957. Date of Electronic Publication: 2019 Apr 11. - Publication Year :
- 2019
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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.<br />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 <superscript>2</superscript> epirubicin and 60 mg/m <superscript>2</superscript> cisplatin on day 1 plus either 200 mg/m <superscript>2</superscript> fluorouracil as continuous intravenous infusion or 1250 mg/m <superscript>2</superscript> capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m <superscript>2</superscript> docetaxel, 85 mg/m <superscript>2</superscript> oxaliplatin, 200 mg/m <superscript>2</superscript> leucovorin and 2600 mg/m <superscript>2</superscript> 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.<br />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.<br />Interpretation: In locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, perioperative FLOT improved overall survival compared with perioperative ECF/ECX.<br />Funding: The German Cancer Aid (Deutsche Krebshilfe), Sanofi-Aventis, Chugai, and Stiftung Leben mit Krebs Foundation.<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adenocarcinoma pathology
Administration, Oral
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Capecitabine administration & dosage
Capecitabine therapeutic use
Cisplatin administration & dosage
Cisplatin therapeutic use
Digestive System Surgical Procedures
Disease-Free Survival
Docetaxel administration & dosage
Docetaxel therapeutic use
Female
Fluorouracil administration & dosage
Fluorouracil therapeutic use
Humans
Leucovorin administration & dosage
Leucovorin therapeutic use
Male
Middle Aged
Neoplasm Staging
Oxaliplatin administration & dosage
Oxaliplatin therapeutic use
Stomach Neoplasms pathology
Treatment Outcome
Adenocarcinoma drug therapy
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Esophagogastric Junction pathology
Stomach Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1474-547X
- Volume :
- 393
- Issue :
- 10184
- Database :
- MEDLINE
- Journal :
- Lancet (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 30982686
- Full Text :
- https://doi.org/10.1016/S0140-6736(18)32557-1