FLOT4

Published

Al-Batran S, et al. "FLOT vs. ECF/ECX for locally advanced, resectable gastric or GEJ adenocarcinoma". The Lancet. 2019. 393(10184):1948-1957.
PubMed • Full text

Clinical Question

Among patients with histologically-confirmed advanced clinical stage cT2 or higher and/or nodal positive stage (cN+) resectable tumours, with no evidence of distant metastases, is FLOT superior to ECX/ECF for overall survival?

Bottom Line

FLOT is superior to ECX/ECF for median overall survival.

Design

• Controlled, open-label, phase 2/3 trial
• N=716
  • FLOT (n=356)
  • ECX/ECF (n=360)
• Setting: 38 German hospitals or with practice-based oncologists
• Enrolment: 2010-2015
• Analysis: Intention-to-treat
• Primary outcomes:
  • Median overall survival [Time Frame: 2 years follow-up]
• Secondary outcomes:
  • Margin-free-(R0) resection rate [Time Frame: 2 years follow-up]
  • Disease-free survival [Time Frame: 2 years follow-up]
  • Surgical morbidity and mortality [Time Frame: up to 2 months after surgery]
  • Adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 3
  • Histopathological regression rate [Time Frame: 6 weeks after surgery]

Population

Inclusion Criteria

• Locally advanced (>T1) and/or nodal positive (N+) histologically proven adenocarcinoma of the esophagogastreal junction (AEG I-III) or the stomach without distant metastases (M0) and without infiltration of adjacent structures and organs
• No previous surgical resection
• No previous cytostatic chemotherapy
• Age > 18 years (female and male)
• ECOG ≤ 2
• Surgical resectability
• Exclusion of peritoneal carcinomatosis (if clinically suspected) via laparoscopy
• Leucocytes > 3.000/µl
• Platelets > 100.000/µl
• Serum creatinin ≤ 1.5x of normal value, or Creatinin-Clearance > 50 ml/min
• Written informed consent.
• Ejection fraction > 50% in echocardiography before start of therapy

Exclusion Criteria

• Distant metastases or infiltration of adjacent structures or organs and all primarily not resectable stages
• Relapse
• Hypersensitivity against 5- Fluorouracil, Leucovorin, Oxaliplatin, Cisplatin. Epirubicin and Docetaxel
• Existence of contraindications against 5- Fluorouracil, Leucovorin, Oxaliplatin, Cisplatin, Epirubicin or Docetaxel
• Active CHD, Cardiomyopathy or cardiac insufficiency stage III-IV according to NYHA
• Malignant secondary disease, dated back < 5 years (exception: In-situ-carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma)
• Severe non-surgical accompanying disease or acute infection
• Peripheral polyneuropathy > NCI Grad II
• Severe liver dysfunction (AST/ALT>3,5xULN, AP>6xULN, Bilirubin>1,5xULN)
• Chronic inflammable gastro-intestinal disease
• Inclusion in another clinical trial
• Pregnancy or lactation