Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma: a safety report

A F C Okines, R E Langley, L C Thompson, S P Stenning, L Stevenson, S Falk, M Seymour, Fraser Coxon, G W Middleton, D Smith, L Evans, S Slater, J Waters, D Ford, M Hall, T J Iveson, R D Petty, C Plummer, W H Allum, J M BlazebyM Griffin, D Cunningham

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Abstract

BACKGROUND: Peri-operative chemotherapy and surgery is a standard treatment of localised oesophagogastric adenocarcinoma; however, the outcomes remain poor.

PATIENTS AND 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.

Original languageEnglish
Pages (from-to)702-709
Number of pages8
JournalAnnals of Oncology
Volume24
Issue number3
Early online date28 Oct 2012
DOIs
Publication statusPublished - Mar 2013

Keywords

  • adenocarcinoma
  • aged
  • antibodies, monoclonal, humanized
  • antineoplastic combined chemotherapy protocols
  • cisplatin
  • deoxycytidine
  • epirubicin
  • esophageal neoplasms
  • female
  • fluorouracil
  • humans
  • male
  • middle aged
  • myocardial infarction
  • stomach neoplasms
  • stroke volume
  • thromboembolism
  • treatment outcome
  • bevacizumab
  • gastric
  • oesophagus
  • peri-operative

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    Okines, A. F. C., Langley, R. E., Thompson, L. C., Stenning, S. P., Stevenson, L., Falk, S., Seymour, M., Coxon, F., Middleton, G. W., Smith, D., Evans, L., Slater, S., Waters, J., Ford, D., Hall, M., Iveson, T. J., Petty, R. D., Plummer, C., Allum, W. H., ... Cunningham, D. (2013). Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma: a safety report. Annals of Oncology, 24(3), 702-709. https://doi.org/10.1093/annonc/mds533