Perioperative chemotherapy with 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) for esophagogastric adenocarcinoma: ten years real-life experience from a surgical perspective

Langenbecks Arch Surg. 2023 Feb 10;408(1):81. doi: 10.1007/s00423-023-02822-7.

Abstract

Purpose: According to the results of FLOT4 trial, perioperative FLOT chemotherapy improved overall survival (OS) in locally advanced, resectable esophagogastric adenocarcinoma (EGA) compared to perioperative ECF/ECX. We report real-life data 10 years after introduction of perioperative FLOT at our institution.

Methods: Survival of 356 consecutive EGA patients (cT3/4 and/or cN + and/or cM1) who underwent curative surgical resection was retrospectively analysed from a prospective database. A total of 263 patients received preoperative chemotherapy according to FLOT protocol and 93 patients received an epirubicin/platinum/5FU-based regimen (EPF). Propensity score matching (PSM) according to pretretment characteristics was performed to compensate for heterogeneity between groups.

Results: Median OS did not differ between groups (FLOT/EPF 52.1/46.4 months, p = 0.577). After PSM, survival was non-significantly improved after FLOT compared to EPF (median OS not reached/46.4 months, p = 0.156). Perioperative morbidity and mortality did not differ between groups. Histopathologic response rate was 35% after FLOT and 26% after EPF (p = 0.169). R0 resection could be achieved more frequently after FLOT than after EPF (93%/79%, p = 0.023).

Conclusion: Overall survival after perioperative FLOT followed by surgery is comparable to clinical trials. However, collective real-life application of FLOT failed to provide a significant survival benefit compared to EPF. In clinical reality, patient selection is triggered by age, comorbidity, tumor localization, and clinical tumor stage. Yet matched analyses support FLOT4 trial findings.

Keywords: Adenocarcinoma; Esophageal cancer; Gastric cancer; Histopathological regression; Perioperative chemotherapy.

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / surgery
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Docetaxel
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / surgery
  • Esophagogastric Junction / pathology
  • Esophagogastric Junction / surgery
  • Fluorouracil
  • Humans
  • Leucovorin
  • Neoadjuvant Therapy
  • Oxaliplatin / therapeutic use
  • Retrospective Studies
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / pathology
  • Stomach Neoplasms* / surgery

Substances

  • Docetaxel
  • Leucovorin
  • Oxaliplatin
  • Fluorouracil