PMID- 29501977
OWN - NLM
STAT- MEDLINE
DCOM- 20190111
LR  - 20190111
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 93
DP  - 2018 Apr
TI  - Perioperative chemotherapy with or without epidermal growth factor 
      receptor blockade in unselected patients with locally advanced oesophagogastric 
      adenocarcinoma: Randomized phase II study with advanced biomarker program of the 
      German Cancer Society (AIO/CAO STO-0801).
PG  - 119-126
LID - S0959-8049(18)30113-8 [pii]
LID - 10.1016/j.ejca.2018.01.079 [doi]
AB  - BACKGROUND: Perioperative chemotherapy significantly improves survival in 
      patients with locally advanced oesophagogastric cancer (EGC). However, as 
      approximately 60% of patients will die from their disease, new therapeutic agents 
      such as molecular-targeted drugs are needed. PATIENTS AND METHODS: To evaluate 
      the role of panitumumab with perioperative chemotherapy, previously untreated 
      patients with locally advanced EGC received, in an open-label randomised phase II 
      study (NEOPECX), standard epirubicin, cisplatin, capecitabine (ECX) chemotherapy 
      with or without panitumumab. The primary end-point was the histological response 
      rate after neoadjuvant therapy. The expression status and gene copy number of 
      EGFR, HER2, and MET were determined by immunohistochemistry and fluorescence in 
      situ hybridization (FISH). Plasma samples were collected before the first cycle 
      of neoadjuvant chemotherapy. RESULTS: Overall, 160 patients (80 versus 80) were 
      eligible. The majority (82% versus 80%) showed lymph node involvement. Rate of 
      R0-resection, percentage of patients with downstaging to ypT0-2 at 
      pathohistological evaluation, and rate of major histological response was equal 
      in both arms. Toxicity was increased by panitumumab with regard to thromboembolic 
      events and skin toxicity. Patients with tumour EGFR, HER2 or MET expression had 
      shorter progression-free and overall survival. FISH positivity for these markers 
      was associated with shorter survival independent of therapy. High levels of 
      soluble EGFR in particular predicted poor survival in the panitumumab arm. 
      CONCLUSION: The addition of panitumumab to ECX did not improve downstaging of 
      locally advanced EGC. Low plasma levels of pathway-associated proteins such as 
      sEGFR may identify a group of patients that benefit from EGFR-directed therapy. 
      CLINICALTRIALS.GOV: NCT01234324.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Stahl, Michael
AU  - Stahl M
AD  - Department of Medical Oncology, Kliniken Essen-Mitte, Essen, Germany.
FAU - Maderer, Annett
AU  - Maderer A
AD  - Department of Internal Medicine II, University Clinic, Mainz, Germany.
FAU - Lordick, Florian
AU  - Lordick F
AD  - University Cancer Center Leipzig (UCCL), University Medicine, Leipzig, Germany.
FAU - Mihaljevic, Andre L
AU  - Mihaljevic AL
AD  - Department of Surgery, Klinikum rechts der Isar, Technische Universitat, Munich, 
      Germany.
FAU - Kanzler, Stefan
AU  - Kanzler S
AD  - Department of Internal Medicine II, Leopoldina Krankenhaus, Schweinfurt, Germany.
FAU - Hoehler, Thomas
AU  - Hoehler T
AD  - Department of Medicine I, Prosper Hospital, Recklinghausen, Germany.
FAU - Thuss-Patience, Peter
AU  - Thuss-Patience P
AD  - Department of Hematology, Oncology and Tumor Immunology, Charite 
      Universitatsmedizin Berlin, Berlin, Germany.
FAU - Monig, Stefan
AU  - Monig S
AD  - Service de chirurgie viscerale, Hopitaux Universitaires Geneve, Geneve, 
      Switzerland.
FAU - Kunzmann, Volker
AU  - Kunzmann V
AD  - Department of Medical Oncology, University Clinic, Wurzburg, Germany.
FAU - Schroll, Sebastian
AU  - Schroll S
AD  - Department of Hematology and Oncology, Klinikum Braunschweig, Germany.
FAU - Sandermann, Andreas
AU  - Sandermann A
AD  - Biostatistics, Wissenschaftlicher Service Pharma GmbH, Langenfeld, Germany.
FAU - Tannapfel, Andrea
AU  - Tannapfel A
AD  - Institute of Pathology, Ruhr-University, Bochum, Germany.
FAU - Meyer, Hans-Joachim
AU  - Meyer HJ
AD  - German Society of Surgery, Berlin, Germany.
FAU - Schuhmacher, Christoph
AU  - Schuhmacher C
AD  - Department of Surgery, Klinikum rechts der Isar, Technische Universitat, Munich, 
      Germany.
FAU - Wilke, Hansjochen
AU  - Wilke H
AD  - Department of Medical Oncology, Kliniken Essen-Mitte, Essen, Germany.
FAU - Moehler, Markus
AU  - Moehler M
AD  - Department of Internal Medicine II, University Clinic, Mainz, Germany. Electronic 
      address: markus.moehler@unimedizin-mainz.de.
CN  - Arbeitsgemeinschaft Internistische Onkologie (AIO) Oesophageal and Gastric Cancer 
      Working Group and the Chirurgische Arbeitsgemeinschaft Onkologie (CAOGI/DGAV) of 
      the German Cancer Society
LA  - eng
SI  - ClinicalTrials.gov/NCT01234324
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180320
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Biomarkers, Tumor)
RN  - 3Z8479ZZ5X (Epirubicin)
RN  - 6804DJ8Z9U (Capecitabine)
RN  - 6A901E312A (Panitumumab)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Adenocarcinoma/drug therapy/*pathology/surgery
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Capecitabine/administration & dosage
MH  - Cisplatin/administration & dosage
MH  - Combined Modality Therapy
MH  - Epirubicin/administration & dosage
MH  - ErbB Receptors/antagonists & inhibitors/genetics
MH  - Esophageal Neoplasms/drug therapy/*pathology/surgery
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Molecular Targeted Therapy
MH  - Mutation
MH  - Neoadjuvant Therapy
MH  - Panitumumab/administration & dosage
MH  - *Perioperative Care
MH  - Prognosis
MH  - Societies, Medical
MH  - Stomach Neoplasms/drug therapy/*pathology/surgery
MH  - Survival Rate
OTO - NOTNLM
OT  - EGFR
OT  - HER2
OT  - MET
OT  - Oesophagogastric adenocarcinoma
OT  - Panitumumab
OT  - Perioperative
EDAT- 2018/03/05 06:00
MHDA- 2019/01/12 06:00
CRDT- 2018/03/05 06:00
PHST- 2017/11/09 00:00 [received]
PHST- 2018/01/11 00:00 [revised]
PHST- 2018/01/18 00:00 [accepted]
PHST- 2018/03/05 06:00 [pubmed]
PHST- 2019/01/12 06:00 [medline]
PHST- 2018/03/05 06:00 [entrez]
AID - S0959-8049(18)30113-8 [pii]
AID - 10.1016/j.ejca.2018.01.079 [doi]
PST - ppublish
SO  - Eur J Cancer. 2018 Apr;93:119-126. doi: 10.1016/j.ejca.2018.01.079. Epub 2018 Mar 
      20.