title: Matuzumab plus epirubicin, cisplatin and capecitabine (ECX) compared with epirubicin, cisplatin and capecitabine alone as first-line treatment in patients with advanced oesophago-gastric cancer: a randomised, multicentre open-label phase II study.
abstract: BACKGROUND
  Clinical data showed promising antitumour activity with feasible tolerability for matuzumab plus epirubicin, cisplatin and capecitabine (ECX) chemotherapy in untreated advanced oesophago-gastric (OG) cancer. The aim was to evaluate the efficacy of matuzumab plus ECX versus ECX alone.
  
  
  METHODS
  In this multicentre, randomised open-label phase II study, 72 patients with metastatic OG cancer were randomly assigned to either 800 mg matuzumab weekly plus epirubicin 50 mg/m², cisplatin 60 mg/m² on day 1 and capecitabine 1250 mg/m² daily in a 21-day cycle (ECX) or the same ECX regimen alone. The primary end point was objective response. Secondary end points included progression-free survival (PFS), overall survival (OS), quality of life, safety and tolerability.
  
  
  RESULTS
  Following random assignment, 35 patients (median age 59 years) received ECX/matuzumab and 36 patients (median age 64 years) ECX. The addition of matuzumab to ECX did not improve objective response: 31% for ECX/matuzumab [95% confidence interval (CI) 17-49] compared with 58% for the ECX arm (95% CI 41-74) P = 0.994 (one sided). There was no significant difference in median PFS: 4.8 months (95% CI 2.9-8.1) for ECX/matuzumab versus 7.1 months (95% CI 4.4-8.5) for ECX, or in median OS: 9.4 months (95% CI 7.5-16.2), compared with 12.2 months (95% CI 9.8-13.8 months). Grade 3/4 treatment-related toxicity was observed in 27 and 25 patients in the ECX/matuzumab and ECX groups, respectively.
  
  
  CONCLUSIONS
  Matuzumab 800 mg weekly combined with ECX chemotherapy does not increase response or survival for patients with advanced OG cancer. Therefore, ECX/matuzumab should not be examined further in phase III trials.
authors.affiliation: Gastrointestinal Unit, Royal Marsden Hospital, London and Surrey, UK.
authors.forename: S
authors.initials: S
authors.lastname: Rao
authors.affiliation: Gastrointestinal Unit, Royal Marsden Hospital, London and Surrey, UK.
authors.forename: N
authors.initials: N
authors.lastname: Starling
authors.affiliation: Gastrointestinal Unit, Royal Marsden Hospital, London and Surrey, UK. Electronic address: david.cunningham@rmh.nhs.uk.
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.affiliation: Oncology Department, Newcastle General Hospital, Newcastle, UK.
authors.forename: K
authors.initials: K
authors.lastname: Sumpter
authors.affiliation: Oncology Department, Addenbrooke's NHS Trust, Cambridge, UK.
authors.forename: D
authors.initials: D
authors.lastname: Gilligan
authors.affiliation: Department of Haematology and Oncology, St Gallen, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Ruhstaller
authors.affiliation: Department of Medical Oncology, Complejo Hospitalario Juan Canalejo, A Coruña, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Valladares-Ayerbes
authors.affiliation: Oncology Department, Kliniken Essen-Mitte, Essen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wilke
authors.affiliation: Oncology Department, St Mary's Hospital, Portsmouth, UK.
authors.forename: C
authors.initials: C
authors.lastname: Archer
authors.affiliation: Gastrointestinal Oncology, Merck Serono, Darmstadt, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kurek
authors.affiliation: Gastrointestinal Oncology, Merck Serono, Darmstadt, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Beadman
authors.affiliation: Gastrointestinal Unit, Royal Marsden Hospital, London and Surrey, UK.
authors.forename: J
authors.initials: J
authors.lastname: Oates
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015251:Epirubicin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D015251:Epirubicin; D000069287:Capecitabine; C520777:matuzumab; D002945:Cisplatin; D005472:Fluorouracil