Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783502230555459584 |
---|---|
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, |
format | Online Article Text |
id | pubmed-7048062 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT fehrmartin highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT hawlehanne highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT hayozstefanie highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT thusspatiencepeter highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT schachersabina highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT rieraknorrenschildjorge highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT durrdonat highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT knoefelwolframt highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT rumpoldholger highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT bitzermichael highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT zweifelmartin highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT samaraspanagiotis highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT meyulrich highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT kungmarc highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT winterhalderralph highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT eistererwolfgang highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT hessviviane highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT gerardmariealine highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT templetonarnoud highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT stahlmichael highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT ruhstallerthomas highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 AT highthromboemboliceventrateinpatientswithlocallyadvancedoesophagealcancerduringneoadjuvanttherapyanexploratoryanalysisoftheprospectiverandomisedintergroupphaseiiitrialsakk7508 |