title: Long-term results and recurrence patterns from SCOPE-1: a phase II/III randomised trial of definitive chemoradiotherapy +/- cetuximab in oesophageal cancer.
abstract: BACKGROUND
  The SCOPE-1 study tested the role of adding cetuximab to conventional definitive chemoradiotherapy (dCRT), and demonstrated greater toxicity and worse survival outcomes. We present the long-term outcomes and patterns of recurrence.
  
  
  METHODS
  SCOPE-1 was a phase II/III trial in which patients were randomised to cisplatin 60 mg m-2(day 1) and capecitabine 625 mg m-2bd (days 1-21) for four cycles +/- cetuximab 400 mg m-2day 1 then by 250 mg m-2weekly. Radiotherapy consisted of 50 Gy/25# given concurrently with cycles 3 and 4. Recruitment was between February 2008 and February 2012, when the IDMC recommended closure on the basis of futility.
  
  
  RESULTS
  About 258 patients (dCRT=129; dCRT+cetuximab (dCRT+C)=129) were recruited from 36 centres. About 72.9% (n=188) had squamous cell histology. The median follow-up (IQR) was 46.2 (35.9-48.3) months for surviving patients. The median overall survival (OS; months; 95% CI) was 34.5 (24.7-42.3) in dCRT and 24.7 (18.6-31.3) in dCRT+C (hazard ratio (HR)=1.25, 95% CIs: 0.93-1.69, P=0.137). Median progression-free survival (PFS; months; 95% CI) was 24.1 (15.3-29.9) and 15.9 (10.7-20.8) months, respectively (HR=1.28, 95% CIs: 0.94-1.75; P=0.114). On multivariable analysis only earlier stage, full-dose RT, and higher cisplatin dose intensity were associated with improved OS.
  
  
  CONCLUSIONS
  The mature analysis demonstrates that the dCRT regimen used in the study provided useful survival outcomes despite its use in patients who were largely unfit for surgery or who had inoperable disease. Given the competing risk of systemic and local failure, future studies should continue to focus on enhancing local control as well as optimising systemic therapy.
authors.affiliation: Velindre Cancer Centre, Velindre Hospital, Cardiff CF14 2TL, UK.
authors.forename: T
authors.initials: T
authors.lastname: Crosby
authors.affiliation: Wales Cancer Trials Unit, Cardiff University, Cardiff CF14 4YS, UK.
authors.forename: C N
authors.initials: CN
authors.lastname: Hurt
authors.affiliation: Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol BS2 8ED, UK.
authors.forename: S
authors.initials: S
authors.lastname: Falk
authors.affiliation: North Wales Cancer Treatment Centre, Conwy and Denbighshire NHS Trust, Rhyl LL18 5UJ, UK.
authors.forename: S
authors.initials: S
authors.lastname: Gollins
authors.affiliation: Velindre Cancer Centre, Velindre Hospital, Cardiff CF14 2TL, UK.
authors.forename: J
authors.initials: J
authors.lastname: Staffurth
authors.affiliation: Wales Cancer Trials Unit, Cardiff University, Cardiff CF14 4YS, UK.
authors.forename: R
authors.initials: R
authors.lastname: Ray
authors.affiliation: UCL Cancer Institute, University College London, London WC1E 6BT, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Bridgewater
authors.affiliation: Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust Birmingham B15 2GW, UK.
authors.forename: J I
authors.initials: JI
authors.lastname: Geh
authors.affiliation: The Royal Marsden Hospital NHS Foundation Trust, London SM2 5PT, UK.
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.affiliation: Centre for Surgical Research, University of Bristol, Bristol BS8 2PS, UK.
authors.forename: J
authors.initials: J
authors.lastname: Blazeby
authors.affiliation: Diana Princess of Wales Hospital, Northern Lincolnshire and Goole NHS Foundation Trust, Grimsby DN33 2BA, UK.
authors.forename: R
authors.initials: R
authors.lastname: Roy
authors.affiliation: CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: T
authors.initials: T
authors.lastname: Maughan
authors.affiliation: Southampton Clinical Trials Unit, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: G
authors.initials: G
authors.lastname: Griffiths
authors.affiliation: CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: S
authors.initials: S
authors.lastname: Mukherjee
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D000068818:Cetuximab / Q000008:administration & dosage; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000473:pathology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000069287:Capecitabine; D000068818:Cetuximab; D002945:Cisplatin