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

2016 ◽  
Vol 34 (5) ◽  
pp. 488-494 ◽  
Author(s):  
Fergus Macbeth ◽  
Simon Noble ◽  
Jessica Evans ◽  
Sheikh Ahmed ◽  
David Cohen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Data Monitoring Committee ◽  
Phase Iii ◽  
Low Molecular Weight ◽  
Cancer Type ◽  
Bleeding Events ◽  
Free Survival ◽  
Survival Difference

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.

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

2018 ◽  
Vol 52 (4) ◽  
pp. 1801220 ◽  
Author(s):  
Guy Meyer ◽  
Benjamin Besse ◽  
Hélène Doubre ◽  
Anaïs Charles-Nelson ◽  
Sandro Aquilanti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Weight ◽  
Overall Survival ◽  
Low Molecular Weight Heparin ◽  
Stage I ◽  
Phase Iii ◽  
Low Molecular Weight ◽  
Significant Difference ◽  
Resected Stage ◽  
Iiia Nsclc

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.

scholarly journals Antitumoral effect of low molecular weight heparin in localized lung cancer. A randomized phase III controlled trial

2017 ◽  
Vol 28 ◽  
pp. x120
Author(s):  
B. Besse ◽  
P. Girard ◽  
H. Doubre ◽  
A. Charles-Nelson ◽  
S. Aquilanti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Controlled Trial ◽  
Phase Iii ◽  
Low Molecular Weight ◽  
Antitumoral Effect

scholarly journals Low-molecular-weight heparin adherence and effects on survival within a randomised phase III lung cancer trial (RASTEN)

2019 ◽  
Vol 118 ◽  
pp. 82-90 ◽  
Author(s):  
E. Gezelius ◽  
P.O. Bendahl ◽  
K. Gonçalves de Oliveira ◽  
L. Ek ◽  
B. Bergman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Phase Iii ◽  
Low Molecular Weight ◽  
Cancer Trial

E-Selectin Inhibitor GMI-1271 Works in Combination with Low-Molecular Weight Heparin to Decrease Venous Thrombosis and Bleeding Risk in a Mouse Model

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 593-593 ◽  
Author(s):  
Daniel Durant Myers ◽  
Shirely K. Wrobleski ◽  
Krus Kelsey ◽  
Diana Farris ◽  
Diaz A. Jose ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thrombosis ◽  
Low Molecular Weight Heparin ◽  
Thrombus Formation ◽  
Dose Range ◽  
Experimental Therapy ◽  
Blood Collection ◽  
Low Molecular Weight ◽  
Carbohydrate Binding ◽  
Bleeding Events

Abstract Background: Previous studies have shown that inhibition of E-selectin can decrease thrombus formation and associated inflammation. E-selectin (CD-62E) is a cell adhesion molecule that is expressed on activated endothelial cells and plays an important role in leukocyte recruitment to the site of vascular injury. GMI-1271 is designed to mimic the bioactive conformation of the sialyl-Lex carbohydrate binding domain of E-selectin and is a specific E-selectin inhibitor. There remains an unmet medical need for a translatable therapeutic that can treat VT in combination with lower, safer levels of low molecular weight heparin (LMWH) anticoagulation. We hypothesize that E-selectin inhibition combined with LMWH will permit lower doses of therapeutic LMWH for the treatment of VT without increasing adverse bleeding events. Methods: Male C57BL/6J mice, 10 weeks old (23-28 grams, n5), underwent our electrolytic IVC model (EIM) to produce a non-occlusive thrombosis, via electrical free radical stimulation (250 µAmp) for 15 minutes. Experimental groups included non-treated controls (CTR-No Tx), animals given LMWH (3-6 mg/kg, SQ, once daily (qd), the E-selectin inhibitor GMI-1271 20/kg intraperitoneal (IP) twice daily (BID), and a combination of the agents. The dose range of LMWH that produced anti-Xa levels in the therapeutic range (0.5-1.0IU/mL) and significantly decreased thrombus weight in this mouse VT model was 5 and 6 mg/kg. Treated mouse groups received the first dose of experimental therapy immediately following thrombus induction and through day 2. Animals were euthanized 2 days post-thrombosis for tissue harvest and blood collection for the following evaluations: thrombus weight (grams), anti-Xa testing, and tail vein bleeding time (seconds). Results: GMI-1271 Works in Combination with LMWH to Decreases Venous Thrombosis : LMWH dosed at 6mg/kg and 5mg/kg alone, significantly decreased venous thrombus weight at 2 days, versus non-treated controls (73.0±7.5, 62.8±1.9 vs. 186.8±63.9 x10-4 grams, P<0.01). Notably, the combination of GMI-1271 20 mg/kg + LMWH 4mg/kg (33% dose decrease from LMWH 6 mg/kg), and GMI-1271 20 mg/kg + LMWH 3mg/kg (50% dose decrease from LMWH 6 mg/kg dose), significantly decreased thrombus weight, versus non-treated controls (75.6±17.1, 73.0±14.8 vs. 186.8±63.9 x10-4 grams, P<0.01), equivalent to the results of higher doses of LMWH alone (FIGURE 1 A). GMI-1271 Does not Increase Bleeding Potential: GMI-1271 administration did not significantly elevate tail bleeding times, versus non-treated control mice (67.00±44 vs. 53.8±7.5 seconds). LMWH dosed at 5mg/kg and 6 mg/kg, elevated tail bleeding times in mice with the 5 mg/kg LMWH group significant versus non-treated controls (87±25 vs. 53.8±7.5 seconds, P<0.005). Both animal groups treated with GMI-1271, in combination with lower dose LMWH therapy, had tail bleeding times comparable to non-treated control animals (FIGURE 1 B). Conclusion: We report, for the first time, that GMI-1271 works in combination with LMWH to significantly reduce acute VT without increasing bleeding times and by inference, bleeding potential. These preliminary studies suggest that E-selectin inhibition with GMI-1271 may be used to treat VT alone, or in combination with lower and safer levels of LMWH anticoagulation. Figure 1 Figure 1. Disclosures Magnani: GlycoMimetics Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Impact of low molecular weight heparin on overall survival in patients with advanced lung cancer: A retrospective study.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e19150-e19150
Author(s):  
Shuchi Gulati ◽  
Mahender Yellu ◽  
Nabeela Iffat Siddiqi ◽  
Jane M. Pruemer ◽  
Changchun Xie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Weight ◽  
Overall Survival ◽  
Retrospective Study ◽  
Low Molecular Weight Heparin ◽  
Advanced Lung Cancer ◽  
Low Molecular Weight
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