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

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

Leila Sisic #  1 , Nerma Crnovrsanin #  1 , Henrik Nienhueser  1 , Jin-On Jung  1   2 , Sabine Schiefer  1 , Georg Martin Haag  3 , Thomas Bruckner  4 , Martin Schneider  1 , Beat P Müller-Stich  1 , Markus W Büchler  1 , Thomas Schmidt  5   6
Affiliations

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

Leila Sisic et al. Langenbecks Arch Surg. .

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.

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Conflict of interest statement

The authors declare no competing interests.

The authors declare that they do not have any commercial interest in the subject of study.

The authors did not receive financial support or funding for conduction of this study.

GM Haag reports fees for advisory role from Sanofi, Roche, Taiho, Nordic, Lilly, Pfizer, honoraria from Roche, travel grants from Amgen, Ipsen and Celgene; research funding is provided by Nordic and Taiho Pharmaceuticals. There is no relationship to the submitted work.

Figures

Fig. 1
Fig. 1
Patient selection and study collective
Fig. 2
Fig. 2
Overall survival according to treatment strategy (perioperative FLOT- vs. epirubicin-based chemotherapy (EPF)) in a all patients, b matched cohorts, c patients without distant metastases (cM0)
Fig. 3
Fig. 3
Treatment effect of FLOT compared to EPF on overall survival according to pretreatment and postoperative patient and tumor characteristics. The forest plot shows hazard ratios for death (oblongs) and 95% confidence intervals (I bars). *Data was not available for all patients; values in bold print indicate a significance-level of p ≤ 0.5
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