title: NeoFLOT: Multicenter phase II study of perioperative chemotherapy in resectable adenocarcinoma of the gastroesophageal junction or gastric adenocarcinoma-Very good response predominantly in patients with intestinal type tumors.
abstract: Perioperative treatment is a standard of care in locally advanced gastroesophageal cancer (GEC) (gastric adenocarcinoma and gastroesophageal junction (GEJ) adenocarcinoma). While preoperative treatment can be applied to the majority of patients, postoperative chemotherapy can be given only to a fraction. The NeoFLOT-study therefore investigates the application of prolonged neoadjuvant chemotherapy (NACT). Patients with T3, T4, and/or node-positive adenocarcinoma (GEC) were eligible for this multicenter phase II trial. NACT consisted of 6 cycles of oxaliplatin 85 mg/m(2) , leucovorin 200 mg/m(2) , 5-fluorouracil 2600 mg/m(2) and docetaxel 50 mg/m(2) (FLOT) applied q 2 wks. Application of adjuvant chemotherapy was explicitly not part of the protocol. R0-resection rate was evaluated as a primary endpoint. Of 59 enrolled patients, 50 patients underwent surgery and were assessable for the primary endpoint. R0-resection rate was 86.0% (43/50). Pathologic complete response (pCR) was 20.0% (10/50) and a further 20% (10/50) of patients achieved near complete histological remission (<10% residual tumor). Among these very good responders, 85% (17/20) had intestinal type tumors, 10% (2/20) had diffuse and 5% (1/20) had mixed type tumors. After 3 cycles of NACT, 6.9% (4/58) of patients developed progressive disease. Median disease-free survival was 32.9 months. The 1-year survival-rate was 79.3%. Grade 3-4 toxicities included neutropenia 29.3%, febrile neutropenia 1.7%, diarrhea 12.1% and mucositis 6.9%. This study indicates that intensified NACT with 6 cycles of FLOT is highly effective and tolerable in resectable GEC. Very good response (pCR and <10% residual tumor) was predominantly observed in patients with intestinal type tumors.
authors.affiliation: Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich, Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schulz
authors.affiliation: Department of Internal Medicine I, Hospital Nordoberpfalz, Weiden, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Kullmann
authors.affiliation: Department of Internal Medicine II, Department of Medical Oncology, University of Würzburg, Würzburg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Kunzmann
authors.affiliation: Department of Gastroenterology, Hepatology and GI-Oncology, Hospital Bogenhausen, München, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Fuchs
authors.affiliation: Department of Medical Oncology, Gastroenterology and Internal Medicine, Hospital Esslingen, Esslingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Geissler
authors.affiliation: Center of Oncology, Landshut, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Vehling-Kaiser
authors.affiliation: Department of Medical Oncology and Hematology, Hospital Barmherzige Brüder, Regensburg, Germany.
authors.forename: Heribert
authors.initials: H
authors.lastname: Stauder
authors.affiliation: Department of Internal Medicine I, University of Erlangen, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Wein
authors.affiliation: University Cancer Center, Krankenhaus Nordwest, Frankfurt, Germany.
authors.forename: Salah-Eddin
authors.initials: SE
authors.lastname: Al-Batran
authors.affiliation: Department of Hematology and Medical Oncology, Klinikum Traunstein, Traunstein, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kubin
authors.affiliation: Department of Internal Medicine II, Hospital Neumarkt i.d.OPf, Neumarkt i.d.OPf, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Schäfer
authors.affiliation: Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich, Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stintzing
authors.affiliation: Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich, Munich, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Giessen
authors.affiliation: Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich, Munich, Germany.
authors.forename: Dominik Paul
authors.initials: DP
authors.lastname: Modest
authors.affiliation: Department of Surgery, Hospital Magdeburg, Magdeburg, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Ridwelski
authors.affiliation: Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich, Munich, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D059035:Perioperative Period; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome
keywords: R0 resection rate; adenocarcinoma of the gastroesophageal junction; gastric cancer; neoadjuvant chemotherapy; pCR