Perioperative Chemotherapy (FLOT Protocol) Compared with Neoadjuvant Chemoradiation (CROSS Protocol) in Patients with Adenocarcinoma of the Esophagus (ESOPEC)

• Applicant: Professor Dr. Jens Höppner
• Subject Area: General and Visceral Surgery
• Term: since 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 264590883

Esophageal adenocarcinoma is among the tumor entities in the western world that are increasing in incidence. In addition to surgical resection, neoadjuvant radiochemotherapy and perioperative chemotherapy are also used extensively in specialized oncological centers. This improves long-term survival: The prospective randomized CROSS study was able to show a significant improvement in overall survival in patients with adenocarcinoma of the esophagus after neoadjuvant chemoradiotherapy and subsequent surgical resection compared to surgery alone. In addition to neoadjuvant chemoradiotherapy, various protocols of perioperative chemotherapy have proven successful in improving survival in gastroesophageal adenocarcinoma. Efficacy, safety, and comparability in terms of overall survival results have been demonstrated for perioperative chemotherapy in small uncontrolled prospective series and retrospective studies for adenocarcinoma of the esophagus. However, there is still a lack of clear evidence of a survival benefit for patients with specific adenocarcinoma of the esophagus, since all successful randomized controlled trials of perioperative chemotherapy are based on mixed patient populations including adenocarcinoma of the esophagus and gastric cancer. The ESOPEC study is carried out to compare the effectiveness of perioperative chemotherapy with the FLOT protocol (5-FU, leucovorin, oxaliplatin, docetaxel) versus the CROSS protocol (41.4Gy + carboplatin, paclitaxel) in esophageal adenocarcinoma. The ESOPEC study prospectively randomized a total of 438 patients with a diagnosis of non-metastatic adenocarcinoma of the esophagus. It randomized 1: 1 into perioperative chemotherapy (FLOT protocol) versus neoadjuvant chemoradiotherapy (CROSS protocol). Surgical resection was performed by thoraco-abdominal esophagectomy or by transabdominal partial esophagectomy with gastrectomy. In addition to overall survival, which serves as the primary endpoint, the disease-free survival time, the pathological regression rates after neoadjuvant therapy, the postoperative pathological tumor stages, the frequency of postoperative pulmonary and operative complications, the treatment-related mortality and the quality of life during and after treatment arms are secondary endpoints. The ESOPEC study has been financially supported by the DFG since 09/2015 and between 2016 and 2020 included and randomized a total of 438 of 438 planned patients. The study has been in the follow-up phase since 10/2020.

• DFG Programme: Clinical Trials
• Co-Investigators: Professor Dr. Thomas Brunner; Professor Dr. Florian Lordick