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High thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. An exploratory analysis of the prospective, randomised intergroup phase III trial SAKK 75/08

BACKGROUND: High rates of venous thromboembolic events (VTEs), mainly in advanced disease, are reported for patients with cancer of the upper gastrointestinal tract (stomach, pancreas) and for treatment with cisplatin. METHODS: Exploratory analysis of VTEs reported as adverse events and serious adve...

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Autores principales: Fehr, Martin, Hawle, Hanne, Hayoz, Stefanie, Thuss-Patience, Peter, Schacher, Sabina, Riera Knorrenschild, Jorge, Dürr, Donat, Knoefel, Wolfram T., Rumpold, Holger, Bitzer, Michael, Zweifel, Martin, Samaras, Panagiotis, Mey, Ulrich, Küng, Marc, Winterhalder, Ralph, Eisterer, Wolfgang, Hess, Viviane, Gérard, Marie-Aline, Templeton, Arnoud, Stahl, Michael, Ruhstaller, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048062/
https://www.ncbi.nlm.nih.gov/pubmed/32111181
http://dx.doi.org/10.1186/s12885-020-6623-z
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author Fehr, Martin
Hawle, Hanne
Hayoz, Stefanie
Thuss-Patience, Peter
Schacher, Sabina
Riera Knorrenschild, Jorge
Dürr, Donat
Knoefel, Wolfram T.
Rumpold, Holger
Bitzer, Michael
Zweifel, Martin
Samaras, Panagiotis
Mey, Ulrich
Küng, Marc
Winterhalder, Ralph
Eisterer, Wolfgang
Hess, Viviane
Gérard, Marie-Aline
Templeton, Arnoud
Stahl, Michael
Ruhstaller, Thomas
author_facet Fehr, Martin
Hawle, Hanne
Hayoz, Stefanie
Thuss-Patience, Peter
Schacher, Sabina
Riera Knorrenschild, Jorge
Dürr, Donat
Knoefel, Wolfram T.
Rumpold, Holger
Bitzer, Michael
Zweifel, Martin
Samaras, Panagiotis
Mey, Ulrich
Küng, Marc
Winterhalder, Ralph
Eisterer, Wolfgang
Hess, Viviane
Gérard, Marie-Aline
Templeton, Arnoud
Stahl, Michael
Ruhstaller, Thomas
author_sort Fehr, Martin
collection PubMed
description BACKGROUND: High rates of venous thromboembolic events (VTEs), mainly in advanced disease, are reported for patients with cancer of the upper gastrointestinal tract (stomach, pancreas) and for treatment with cisplatin. METHODS: Exploratory analysis of VTEs reported as adverse events and serious adverse events in a prospective, randomised, multicentre, multimodal phase III trial according to VTEs reported as adverse events and severe adverse events. Patients with resectable oesophageal cancer (T2N1–3, T3-4aNx) were randomized to 2 cycles of chemotherapy with docetaxel 75 mg/m(2), cisplatin 75 mg/m(2) followed by chemo-radiotherapy (CRT) and subsequent surgery (control arm) or the same treatment with addition of cetuximab (investigational arm). RESULTS: VTEs occurred in 26 of 300 patients included in the trial, resulting in an incidence rate (IR) of 8.7% [95% CI 5.7–12.4%]. A total of 29 VTEs were reported:13 (45%) VTEs were grade 2, 13 (45%) grade 3 and three (10%) fatal grade 5 events. 72% (21/29) of all VTEs occurred preoperatively (IR 6.7%): 14% (4/29) during chemotherapy and 59% (17/29) during CRT. In multivariable logistic regression only adenocarcinoma (IR 11.1%, 21/189 patients) compared to squamous cell cancer (IR 4.5%, 5/111 patients) was significantly associated with VTE-risk during treatment, OR 2.9 [95%CI 1.0–8.4], p = 0.046. Baseline Khorana risk score was 0 in 73% (19/26), 1–2 in 23% (6/26) and 3 in only 4% (1/26) of patients with VTEs. CONCLUSION: A high incidence of VTEs during preoperative therapy of resectable oesophageal cancer is observed in this analysis, especially in patients with adenocarcinoma. The role of prophylactic anticoagulation during neoadjuvant therapy in resectable esophageal cancer should be further evaluated in prospective clinical trials. According to our data, which are in line with other analysis of VTE-risk in patients with oesophageal cancer patients treated with neoadjuvant cisplatin-based chemotherapy and CRT, prophylactic anticoagluation could be considered balanced against individual bleeding risks, especially in patients with adenocarcinoma. In addition to the established risk factors, oesophageal adenocarcinoma treated with neoadjuvant cisplatin-based therapy may be regarded as a high-risk situation for VTEs. TRIAL REGISTRATION: Registered at clinicaltrials.gov, NCT01107639, on 21 April 2010,
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spelling pubmed-70480622020-03-05 High thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. An exploratory analysis of the prospective, randomised intergroup phase III trial SAKK 75/08 Fehr, Martin Hawle, Hanne Hayoz, Stefanie Thuss-Patience, Peter Schacher, Sabina Riera Knorrenschild, Jorge Dürr, Donat Knoefel, Wolfram T. Rumpold, Holger Bitzer, Michael Zweifel, Martin Samaras, Panagiotis Mey, Ulrich Küng, Marc Winterhalder, Ralph Eisterer, Wolfgang Hess, Viviane Gérard, Marie-Aline Templeton, Arnoud Stahl, Michael Ruhstaller, Thomas BMC Cancer Research Article BACKGROUND: High rates of venous thromboembolic events (VTEs), mainly in advanced disease, are reported for patients with cancer of the upper gastrointestinal tract (stomach, pancreas) and for treatment with cisplatin. METHODS: Exploratory analysis of VTEs reported as adverse events and serious adverse events in a prospective, randomised, multicentre, multimodal phase III trial according to VTEs reported as adverse events and severe adverse events. Patients with resectable oesophageal cancer (T2N1–3, T3-4aNx) were randomized to 2 cycles of chemotherapy with docetaxel 75 mg/m(2), cisplatin 75 mg/m(2) followed by chemo-radiotherapy (CRT) and subsequent surgery (control arm) or the same treatment with addition of cetuximab (investigational arm). RESULTS: VTEs occurred in 26 of 300 patients included in the trial, resulting in an incidence rate (IR) of 8.7% [95% CI 5.7–12.4%]. A total of 29 VTEs were reported:13 (45%) VTEs were grade 2, 13 (45%) grade 3 and three (10%) fatal grade 5 events. 72% (21/29) of all VTEs occurred preoperatively (IR 6.7%): 14% (4/29) during chemotherapy and 59% (17/29) during CRT. In multivariable logistic regression only adenocarcinoma (IR 11.1%, 21/189 patients) compared to squamous cell cancer (IR 4.5%, 5/111 patients) was significantly associated with VTE-risk during treatment, OR 2.9 [95%CI 1.0–8.4], p = 0.046. Baseline Khorana risk score was 0 in 73% (19/26), 1–2 in 23% (6/26) and 3 in only 4% (1/26) of patients with VTEs. CONCLUSION: A high incidence of VTEs during preoperative therapy of resectable oesophageal cancer is observed in this analysis, especially in patients with adenocarcinoma. The role of prophylactic anticoagulation during neoadjuvant therapy in resectable esophageal cancer should be further evaluated in prospective clinical trials. According to our data, which are in line with other analysis of VTE-risk in patients with oesophageal cancer patients treated with neoadjuvant cisplatin-based chemotherapy and CRT, prophylactic anticoagluation could be considered balanced against individual bleeding risks, especially in patients with adenocarcinoma. In addition to the established risk factors, oesophageal adenocarcinoma treated with neoadjuvant cisplatin-based therapy may be regarded as a high-risk situation for VTEs. TRIAL REGISTRATION: Registered at clinicaltrials.gov, NCT01107639, on 21 April 2010, BioMed Central 2020-02-28 /pmc/articles/PMC7048062/ /pubmed/32111181 http://dx.doi.org/10.1186/s12885-020-6623-z Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Fehr, Martin
Hawle, Hanne
Hayoz, Stefanie
Thuss-Patience, Peter
Schacher, Sabina
Riera Knorrenschild, Jorge
Dürr, Donat
Knoefel, Wolfram T.
Rumpold, Holger
Bitzer, Michael
Zweifel, Martin
Samaras, Panagiotis
Mey, Ulrich
Küng, Marc
Winterhalder, Ralph
Eisterer, Wolfgang
Hess, Viviane
Gérard, Marie-Aline
Templeton, Arnoud
Stahl, Michael
Ruhstaller, Thomas
High thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. An exploratory analysis of the prospective, randomised intergroup phase III trial SAKK 75/08
title High thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. An exploratory analysis of the prospective, randomised intergroup phase III trial SAKK 75/08
title_full High thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. An exploratory analysis of the prospective, randomised intergroup phase III trial SAKK 75/08
title_fullStr High thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. An exploratory analysis of the prospective, randomised intergroup phase III trial SAKK 75/08
title_full_unstemmed High thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. An exploratory analysis of the prospective, randomised intergroup phase III trial SAKK 75/08
title_short High thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. An exploratory analysis of the prospective, randomised intergroup phase III trial SAKK 75/08
title_sort high thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. an exploratory analysis of the prospective, randomised intergroup phase iii trial sakk 75/08
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048062/
https://www.ncbi.nlm.nih.gov/pubmed/32111181
http://dx.doi.org/10.1186/s12885-020-6623-z
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