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 & 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
    Article numbermds533
    Pages (from-to)702-709
    Number of pages8
    JournalAnnals of Oncology
    Volume24
    Issue number3
    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
    Bevacizumab
    Capecitabine
    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

    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. [mds533]. 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, 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. ; 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.
    @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",
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    doi = "10.1093/annonc/mds533",
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    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

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

    In: Annals of Oncology, Vol. 24, No. 3, mds533, 03.2013, p. 702-709.

    Research output: Contribution to journalArticle

    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

    VL - 24

    SP - 702

    EP - 709

    JO - Annals of Oncology

    JF - Annals of Oncology

    SN - 0923-7534

    IS - 3

    M1 - mds533

    ER -