Anti-tumour effect of low molecular weight heparin in localised lung cancer: A phase III clinical trial

Guy Meyer; Benjamin Besse; Hélène Doubre; Anaïs Charles-Nelson; Sandro Aquilanti; Armine Izadifar; Reza Azarian; Isabelle Monnet; Corinne Lamour; Renaud Descourt; Gérard Oliviero; Laurent Taillade; Christos Chouaid; Frederique Giraud; Pierre Emmanuel Falcoz; Marie Pierre Revel; Virginie Westeel; Adrien Dixmier; Jean Tredaniel; Stéphanie Dehette; Chantal Decroisette; Alain Prevost; Eric Pichon; Elizabeth Fabre; Jean Charles Soria; Sylvie Friard; Jean Baptiste Stern; Laurence Jabot; Georges Dennewald; Gérard Pavy; Patrick Petitpretz; Jean Marc Tourani; Marco Alifano; Gilles Chatellier; Philippe Girard

doi:10.1183/13993003.01220-2018

Anti-tumour effect of low molecular weight heparin in localised lung cancer: A phase III clinical trial

Guy Meyer, Benjamin Besse, Hélène Doubre, Anaïs Charles-Nelson, Sandro Aquilanti, Armine Izadifar, Reza Azarian, Isabelle Monnet, Corinne Lamour, Renaud Descourt, Gérard Oliviero, Laurent Taillade, Christos Chouaid, Frederique Giraud, Pierre Emmanuel Falcoz, Marie Pierre Revel, Virginie Westeel, Adrien Dixmier, Jean Tredaniel, Stéphanie DehetteChantal Decroisette, Alain Prevost, Eric Pichon, Elizabeth Fabre, Jean Charles Soria, Sylvie Friard, Jean Baptiste Stern, Laurence Jabot, Georges Dennewald, Gérard Pavy, Patrick Petitpretz, Jean Marc Tourani, Marco Alifano, Gilles Chatellier, Philippe Girard

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Abstract

The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated. Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg⁻¹ once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival. In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±SD age was 61.6±8.9 years, 190 (34.6%) patients had stage II−III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92–1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68–1.30; p=0.70). Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I−IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents.

Original language	English
Article number	1801220
Journal	European Respiratory Journal
Volume	52
Issue number	4
DOIs	https://doi.org/10.1183/13993003.01220-2018
Publication status	Published - 1 Oct 2018

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Meyer, G., Besse, B., Doubre, H., Charles-Nelson, A., Aquilanti, S., Izadifar, A., Azarian, R., Monnet, I., Lamour, C., Descourt, R., Oliviero, G., Taillade, L., Chouaid, C., Giraud, F., Falcoz, P. E., Revel, M. P., Westeel, V., Dixmier, A., Tredaniel, J., ... Girard, P. (2018). Anti-tumour effect of low molecular weight heparin in localised lung cancer: A phase III clinical trial. European Respiratory Journal, 52(4), Article 1801220. https://doi.org/10.1183/13993003.01220-2018

@article{8db7ab6369354ada9f089ce487698a67,

title = "Anti-tumour effect of low molecular weight heparin in localised lung cancer: A phase III clinical trial",

abstract = "The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated. Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg−1 once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival. In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±SD age was 61.6±8.9 years, 190 (34.6%) patients had stage II−III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92–1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68–1.30; p=0.70). Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I−IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents.",

author = "Guy Meyer and Benjamin Besse and H{\'e}l{\`e}ne Doubre and Ana{\"i}s Charles-Nelson and Sandro Aquilanti and Armine Izadifar and Reza Azarian and Isabelle Monnet and Corinne Lamour and Renaud Descourt and G{\'e}rard Oliviero and Laurent Taillade and Christos Chouaid and Frederique Giraud and Falcoz, {Pierre Emmanuel} and Revel, {Marie Pierre} and Virginie Westeel and Adrien Dixmier and Jean Tredaniel and St{\'e}phanie Dehette and Chantal Decroisette and Alain Prevost and Eric Pichon and Elizabeth Fabre and Soria, {Jean Charles} and Sylvie Friard and Stern, {Jean Baptiste} and Laurence Jabot and Georges Dennewald and G{\'e}rard Pavy and Patrick Petitpretz and Tourani, {Jean Marc} and Marco Alifano and Gilles Chatellier and Philippe Girard",

note = "Publisher Copyright: Copyright {\textcopyright}ERS 2018.",

year = "2018",

month = oct,

day = "1",

doi = "10.1183/13993003.01220-2018",

language = "English",

volume = "52",

journal = "European Respiratory Journal",

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Meyer, G, Besse, B, Doubre, H, Charles-Nelson, A, Aquilanti, S, Izadifar, A, Azarian, R, Monnet, I, Lamour, C, Descourt, R, Oliviero, G, Taillade, L, Chouaid, C, Giraud, F, Falcoz, PE, Revel, MP, Westeel, V, Dixmier, A, Tredaniel, J, Dehette, S, Decroisette, C, Prevost, A, Pichon, E, Fabre, E, Soria, JC, Friard, S, Stern, JB, Jabot, L, Dennewald, G, Pavy, G, Petitpretz, P, Tourani, JM, Alifano, M, Chatellier, G & Girard, P 2018, 'Anti-tumour effect of low molecular weight heparin in localised lung cancer: A phase III clinical trial', European Respiratory Journal, vol. 52, no. 4, 1801220. https://doi.org/10.1183/13993003.01220-2018

TY - JOUR

T1 - Anti-tumour effect of low molecular weight heparin in localised lung cancer

T2 - A phase III clinical trial

AU - Meyer, Guy

AU - Besse, Benjamin

AU - Doubre, Hélène

AU - Charles-Nelson, Anaïs

AU - Aquilanti, Sandro

AU - Izadifar, Armine

AU - Azarian, Reza

AU - Monnet, Isabelle

AU - Lamour, Corinne

AU - Descourt, Renaud

AU - Oliviero, Gérard

AU - Taillade, Laurent

AU - Chouaid, Christos

AU - Giraud, Frederique

AU - Falcoz, Pierre Emmanuel

AU - Revel, Marie Pierre

AU - Westeel, Virginie

AU - Dixmier, Adrien

AU - Tredaniel, Jean

AU - Dehette, Stéphanie

AU - Decroisette, Chantal

AU - Prevost, Alain

AU - Pichon, Eric

AU - Fabre, Elizabeth

AU - Soria, Jean Charles

AU - Friard, Sylvie

AU - Stern, Jean Baptiste

AU - Jabot, Laurence

AU - Dennewald, Georges

AU - Pavy, Gérard

AU - Petitpretz, Patrick

AU - Tourani, Jean Marc

AU - Alifano, Marco

AU - Chatellier, Gilles

AU - Girard, Philippe

PY - 2018/10/1

Y1 - 2018/10/1

N2 - The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated. Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg−1 once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival. In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±SD age was 61.6±8.9 years, 190 (34.6%) patients had stage II−III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92–1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68–1.30; p=0.70). Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I−IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents.

AB - The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated. Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg−1 once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival. In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±SD age was 61.6±8.9 years, 190 (34.6%) patients had stage II−III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92–1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68–1.30; p=0.70). Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I−IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents.

UR - http://www.scopus.com/inward/record.url?scp=85054423702&partnerID=8YFLogxK

U2 - 10.1183/13993003.01220-2018

DO - 10.1183/13993003.01220-2018

M3 - Article

C2 - 30262574

AN - SCOPUS:85054423702

SN - 0903-1936

VL - 52

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 4

M1 - 1801220

ER -

Anti-tumour effect of low molecular weight heparin in localised lung cancer: A phase III clinical trial

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