title: Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma: a safety report.
abstract: BACKGROUND
  Peri-operative chemotherapy and surgery is a standard treatment of localised oesophagogastric adenocarcinoma; however, the outcomes remain poor.
  
  
  METHODS
  ST03 is a multicentre, randomised, phase II/III study comparing peri-operative ECX with or without bevacizumab (ECX-B). The primary outcome measure of phase II (n = 200) was safety, specifically gastrointestinal (GI) perforation rates and cardiotoxicity.
  
  
  RESULTS
  Two hundred patients were randomised between October 2007 and April 2010. Ninety-one/101 (90%) ECX and 86/99 (87%) ECX-B patients completed pre-operative chemotherapy; 7 ECX and 9 ECX-B patients stopped due to toxicity. Gastrointestinal perforations (3 ECX, 1 ECX-B), cardiac events (1 ECX, 4 ECX-B) and venous thromboembolic events (VTEs, 8 ECX, 7 ECX-B) were uncommon. Arterial thromboembolic events (ATEs, myocardial infarction (MI) or cerebrovascular accident) were more frequent with ECX-B (5 versus 1 with ECX). Delayed wound healing, anastomotic leaks and GI bleeding rates were similar. More asymptomatic left ventricular ejection fraction (LVEF) falls (≥15% and/or to <50%) occurred with ECX-B (21.2% versus 11.1% with ECX). Clinically significant falls (≥10% to below lower limit of normal, LLN) occurred in (15.3%) and (8.9%) respectively, with no associated cardiac failure (median 22 months follow-up).
  
  
  CONCLUSIONS
  Addition of bevacizumab to peri-operative ECX chemotherapy is feasible with acceptable toxicity and no negative impact on surgical outcomes.
authors.affiliation: Department of Medicine, The Royal Marsden Hospital NHS Foundation Trust London & Surrey SM2 5PT, London.
authors.forename: A F C
authors.initials: AF
authors.lastname: Okines
authors.forename: R E
authors.initials: RE
authors.lastname: Langley
authors.forename: L C
authors.initials: LC
authors.lastname: Thompson
authors.forename: S P
authors.initials: SP
authors.lastname: Stenning
authors.forename: L
authors.initials: L
authors.lastname: Stevenson
authors.forename: S
authors.initials: S
authors.lastname: Falk
authors.forename: M
authors.initials: M
authors.lastname: Seymour
authors.forename: F
authors.initials: F
authors.lastname: Coxon
authors.forename: G W
authors.initials: GW
authors.lastname: Middleton
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.forename: L
authors.initials: L
authors.lastname: Evans
authors.forename: S
authors.initials: S
authors.lastname: Slater
authors.forename: J
authors.initials: J
authors.lastname: Waters
authors.forename: D
authors.initials: D
authors.lastname: Ford
authors.forename: M
authors.initials: M
authors.lastname: Hall
authors.forename: T J
authors.initials: TJ
authors.lastname: Iveson
authors.forename: R D
authors.initials: RD
authors.lastname: Petty
authors.forename: C
authors.initials: C
authors.lastname: Plummer
authors.forename: W H
authors.initials: WH
authors.lastname: Allum
authors.forename: J M
authors.initials: JM
authors.lastname: Blazeby
authors.forename: M
authors.initials: M
authors.lastname: Griffin
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000601:surgery; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D000068258:Bevacizumab; 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* / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced / Q000503:physiopathology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000601:surgery; D013318:Stroke Volume / Q000187:drug effects; D013923:Thromboembolism / Q000139:chemically induced / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D015251:Epirubicin; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil