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.
Abstract
Whether the antimetastatic properties of heparins benefit patients with early-stage cancer is unknown. In this phase III trial, adjuvant tinzaparin in patients with resected lung cancer had no impact on overall survival and tumour recurrence. http://ow.ly/RZt030lpCuQ
Footnotes
Published online October 4, 2018; republished October 10, 2018 with amendments to the conflict of interest disclosure statement.
This article has supplementary material available from erj.ersjournals.com
Presented in part during the XXVI meeting of the International Society on Thrombosis and Haemostasis, in Berlin, July 12, 2017.
This study is registered at ClinicalTrials.gov with identifier number NCT00475098. Requests for individual de-identified participant data, study protocol and statistical analysis plan should be sent to G. Meyer (guy.meyer@aphp.fr) or G. Chatellier (gilles.chatellier@aphp.fr).
Author contributions: G. Meyer, P. Girard and M. Alifano are the coordinating investigators of the TILT trial, they made substantial contributions to the conception and design of the trial, drafted the manuscript, and revised the manuscript critically for important intellectual content. G. Chatellier made substantial contributions to the conception and design of the trial, drafted the manuscript, and revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Conflict of interest: G. Meyer reports grants and non-financial support from Leo Pharma, outside the submitted work.
Conflict of interest: B. Besse has nothing to disclose.
Conflict of interest: H. Doubre has nothing to disclose.
Conflict of interest: A. Charles-Nelson has nothing to disclose.
Conflict of interest: S. Aquilanti reports non-financial support from Leo Pharma, outside the submitted work.
Conflict of interest: A. Izadifar has nothing to disclose.
Conflict of interest: R. Azarian has nothing to disclose.
Conflict of interest: I. Monnet has nothing to disclose.
Conflict of interest: C. Lamour has nothing to disclose.
Conflict of interest: R. Descourt has nothing to disclose.
Conflict of interest: G. Oliviero has nothing to disclose.
Conflict of interest: L. Taillade has nothing to disclose.
Conflict of interest: C. Chouaid has nothing to disclose.
Conflict of interest: F. Giraud has nothing to disclose.
Conflict of interest: P-E. Falcoz has nothing to disclose.
Conflict of interest: M-P. Revel has nothing to disclose.
Conflict of interest: V. Westeel has nothing to disclose.
Conflict of interest: A. Dixmier has nothing to disclose.
Conflict of interest: J. Tredaniel has nothing to disclose.
Conflict of interest: S. Dehette has nothing to disclose.
Conflict of interest: C. Decroisette has nothing to disclose.
Conflict of interest: A. Prevost has nothing to disclose.
Conflict of interest: E. Pichon has nothing to disclose.
Conflict of interest: E. Fabre has nothing to disclose.
Conflict of interest: J-C. Soria is a full time employee at Medimmune (this position was undertaken after completion of the study), and has received consultancy fees from AstraZeneca, Roche, Sanofi, Servier, Abbvie and Pharmamar, outside the submitted work.
Conflict of interest: S. Friard has nothing to disclose.
Conflict of interest: J-B. Stern has nothing to disclose.
Conflict of interest: L. Jabot has nothing to disclose.
Conflict of interest: G. Dennewald has nothing to disclose.
Conflict of interest: G. Pavy has nothing to disclose.
Conflict of interest: P. Petitpretz has nothing to disclose.
Conflict of interest: J-M. Tourani has nothing to disclose.
Conflict of interest: M. Alifano has nothing to disclose.
Conflict of interest: Dr. Chatellier has nothing to disclose.
Conflict of interest: P. Girard reports personal fees and non-financial support from Leo Pharma, outside the submitted work.
Support statement: The trial was sponsored by the Assistance Publique-Hôpitaux de Paris and funded by two grants from the Programme Hospitalier de Recherche Clinique, French Ministry of Health, (PHRC AOM05185 and PHRC AOM12612). Leo Pharma provided the drug and an additional grant. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received June 30, 2018.
- Accepted August 6, 2018.
- Copyright ©ERS 2018
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