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; F. 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; M. Griffin; D. Cunningham

doi:10.1093/annonc/mds533

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
, F. 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

M. Griffin, D. Cunningham (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

62 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 language	English
Article number	mds533
Pages (from-to)	702-709
Number of pages	8
Journal	Annals of Oncology
Volume	24
Issue number	3
DOIs	https://doi.org/10.1093/annonc/mds533
Publication status	Published - 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

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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. Article mds533. https://doi.org/10.1093/annonc/mds533

@article{549942a10d184eb68b4a5a4b2b102502,

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.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.",

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",

author = "Okines, \{A. F. C.\} and Langley, \{R. E.\} and Thompson, \{L. C.\} and Stenning, \{S. P.\} and L. Stevenson and S. Falk and M. Seymour and F. Coxon and Middleton, \{G. W.\} and D. Smith and L. Evans and S. Slater and J. Waters and D. Ford and M. Hall and Iveson, \{T. J.\} and Petty, \{R. D.\} and C. Plummer and Allum, \{W. H.\} and Blazeby, \{J. M.\} and M. Griffin and D. Cunningham",

year = "2013",

month = mar,

doi = "10.1093/annonc/mds533",

language = "English",

volume = "24",

pages = "702--709",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Elsevier",

number = "3",

}

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, mds533, pp. 702-709. https://doi.org/10.1093/annonc/mds533

TY - JOUR

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, F.

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.

PY - 2013/3

Y1 - 2013/3

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

U2 - 10.1093/annonc/mds533

DO - 10.1093/annonc/mds533

M3 - Article

C2 - 23108952

SN - 0923-7534

VL - 24

SP - 702

EP - 709

JO - Annals of Oncology

JF - Annals of Oncology

IS - 3

M1 - mds533

ER -

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

Abstract

Keywords

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