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J Clin Oncol. 2016 Feb 10;34(5):488-94. doi: 10.1200/JCO.2015.64.0268. Epub 2015 Dec 23.

Randomized Phase III Trial of Standard Therapy Plus Low Molecular Weight Heparin in Patients With Lung Cancer: FRAGMATIC Trial.

Author information

1
Fergus Macbeth, Jessica Evans, Sheikh Ahmed, and Gareth Griffiths, Wales Cancer Trials Unit; Simon Noble and Kerenza Hood, Cardiff University; David Cohen and Mirella Longo, University of South Wales; Barbara Moore, National Institute for Social Care and Health Research Clinical Research Centre, Cardiff; Gareth Griffiths, University of Southampton, Southampton; Dana Knoyle, Prince Charles Hospital, Merthyr Tydfil; Penella J. Woll, Weston Park Hospital, Sheffield; Wiebke Appel, Royal Preston Hospital, Preston; Jeanette Dickson, Mount Vernon Cancer Center, Northwood; David Ferry, Royal Wolverhampton Hospitals National Health Service Trust, Wolverhampton; Caroline Brammer, Mid Staffordshire Hospital, Stafford, United Kingdom; and Seamus Linnane, Beaumont Hospital, Dublin, Ireland. fragmatic@cardiff.ac.uk.
2
Fergus Macbeth, Jessica Evans, Sheikh Ahmed, and Gareth Griffiths, Wales Cancer Trials Unit; Simon Noble and Kerenza Hood, Cardiff University; David Cohen and Mirella Longo, University of South Wales; Barbara Moore, National Institute for Social Care and Health Research Clinical Research Centre, Cardiff; Gareth Griffiths, University of Southampton, Southampton; Dana Knoyle, Prince Charles Hospital, Merthyr Tydfil; Penella J. Woll, Weston Park Hospital, Sheffield; Wiebke Appel, Royal Preston Hospital, Preston; Jeanette Dickson, Mount Vernon Cancer Center, Northwood; David Ferry, Royal Wolverhampton Hospitals National Health Service Trust, Wolverhampton; Caroline Brammer, Mid Staffordshire Hospital, Stafford, United Kingdom; and Seamus Linnane, Beaumont Hospital, Dublin, Ireland.

Abstract

PURPOSE:

Venous thromboembolism (VTE) is common in cancer patients. Evidence has suggested that low molecular weight heparin (LMWH) might improve survival in patients with cancer by preventing both VTE and the progression of metastases. No trial in a single cancer type has been powered to demonstrate a clinically significant survival difference. The aim of this trial was to investigate this question in patients with lung cancer.

PATIENTS AND METHODS:

We conducted a multicenter, open-label, randomized trial to evaluate the addition of a primary prophylactic dose of LMWH for 24 weeks to standard treatment in patients with newly diagnosed lung cancer of any stage and histology. The primary outcome was 1-year survival. Secondary outcomes included metastasis-free survival, VTE-free survival, toxicity, and quality of life.

RESULTS:

For this trial, 2,202 patients were randomly assigned to the two treatment arms over 4 years. The trial did not reach its intended number of events for the primary analysis (2,047 deaths), and data were analyzed after 2,013 deaths after discussion with the independent data monitoring committee. There was no evidence of a difference in overall or metastasis-free survival between the two arms (hazard ratio [HR], 1.01; 95% CI, 0.93 to 1.10; P = .814; and HR, 0.99; 95% CI, 0.91 to 1.08; P = .864, respectively). There was a reduction in the risk of VTE from 9.7% to 5.5% (HR, 0.57; 95% CI, 0.42 to 0.79; P = .001) in the LMWH arm and no difference in major bleeding events but evidence of an increase in the composite of major and clinically relevant nonmajor bleeding in the LMWH arm.

CONCLUSION:

LMWH did not improve overall survival in the patients with lung cancer in this trial. A significant reduction in VTE is associated with an increase in clinically relevant nonmajor bleeding. Strategies to target those at greatest risk of VTE are warranted.

PMID:
26700124
DOI:
10.1200/JCO.2015.64.0268
[Indexed for MEDLINE]
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