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 Blazeby & 2 others M Griffin, D Cunningham

Research output: Contribution to journalArticle

49 Citations (Scopus)

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

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Epirubicin
Cisplatin
Adenocarcinoma
Safety
Drug Therapy
Anastomotic Leak
Stroke Volume
Wound Healing
Heart Failure
Stroke
Myocardial Infarction
Outcome Assessment (Health Care)
Hemorrhage
Capecitabine
Bevacizumab
Therapeutics

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

Cite this

Okines, A. F. C., Langley, R. E., Thompson, L. C., Stenning, S. P., Stevenson, L., Falk, S., ... 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

Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma : a safety report. / Okines, A F C; Langley, R E; Thompson, L C; Stenning, S P; Stevenson, L; Falk, S; Seymour, M; Coxon, Fraser; 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; Blazeby, J M; Griffin, M; Cunningham, D.

In: Annals of Oncology, Vol. 24, No. 3, 03.2013, p. 702-709.

Research output: Contribution to journalArticle

Okines, AFC, Langley, RE, Thompson, LC, Stenning, SP, Stevenson, L, Falk, S, Seymour, M, Coxon, F, Middleton, GW, Smith, D, Evans, L, Slater, S, Waters, J, Ford, D, Hall, M, Iveson, TJ, Petty, RD, Plummer, C, Allum, WH, Blazeby, JM, Griffin, M & Cunningham, D 2013, 'Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma: a safety report', Annals of Oncology, vol. 24, no. 3, pp. 702-709. https://doi.org/10.1093/annonc/mds533
Okines, A F C ; Langley, R E ; Thompson, L C ; Stenning, S P ; Stevenson, L ; Falk, S ; Seymour, M ; Coxon, Fraser ; 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 ; Blazeby, J M ; Griffin, M ; Cunningham, D. / Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma : a safety report. In: Annals of Oncology. 2013 ; Vol. 24, No. 3. pp. 702-709.
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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.",
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T1 - Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma

T2 - a safety report

AU - Okines, A F C

AU - Langley, R E

AU - Thompson, L C

AU - Stenning, S P

AU - Stevenson, L

AU - Falk, S

AU - Seymour, M

AU - Coxon, Fraser

AU - Middleton, G W

AU - Smith, D

AU - Evans, L

AU - Slater, S

AU - Waters, J

AU - Ford, D

AU - Hall, M

AU - Iveson, T J

AU - Petty, R D

AU - Plummer, C

AU - Allum, W H

AU - Blazeby, J M

AU - Griffin, M

AU - Cunningham, D

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N2 - 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.

AB - 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.

KW - adenocarcinoma

KW - aged

KW - antibodies, monoclonal, humanized

KW - antineoplastic combined chemotherapy protocols

KW - cisplatin

KW - deoxycytidine

KW - epirubicin

KW - esophageal neoplasms

KW - female

KW - fluorouracil

KW - humans

KW - male

KW - middle aged

KW - myocardial infarction

KW - stomach neoplasms

KW - stroke volume

KW - thromboembolism

KW - treatment outcome

KW - bevacizumab

KW - gastric

KW - oesophagus

KW - peri-operative

U2 - 10.1093/annonc/mds533

DO - 10.1093/annonc/mds533

M3 - Article

VL - 24

SP - 702

EP - 709

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 3

ER -