TY - JOUR
T1 - Randomized Phase III Trial of Low Molecular Weight Heparin Enoxaparin in Addition to Standard Treatment in Small Cell Lung Cancer
T2 - the RASTEN Trial
AU - Ek, L
AU - Gezelius, E
AU - Bergman, B
AU - Bendahl, P O
AU - Anderson, H
AU - Sundberg, J
AU - Wallberg, M
AU - Falkmer, U
AU - Verma, S
AU - Belting, M
AU - Swedish Lung Cancer Study Group (SLUSG)
N1 - © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Background: Coagulation activation and venous thromboembolism (VTE) are hallmarks of malignant disease and represent a major cause of morbidity and mortality in cancer. Coagulation inhibition with low molecular weight heparin (LMWH) may improve survival specifically in small cell lung cancer (SCLC) patients by preventing VTE and tumor progression; however, randomized trials with well-defined patient populations are needed to obtain conclusive data. The aim of RASTEN was to investigate the survival effect of LMWH enoxaparin in a homogenous population of SCLC patients.Patients and Methods: We performed a randomized, multicenter, open-label trial to investigate the addition of enoxaparin at a supraprophylactic dose (1 mg/kg) to standard treatment in patients with newly diagnosed SCLC. The primary outcome was overall survival (OS), and secondary outcomes were progression-free survival (PFS), incidence of VTE and hemorrhagic events.Results: In RASTEN, 390 patients were randomized over an 8-year period (2008-2016), of which 186 and 191 were included in the final analysis in the LMWH and control arm, respectively. We found no evidence of a difference in OS or PFS by the addition of enoxaparin (HR 1.11; 95% CI: 0.89-1.38, P=0.36 and HR 1.18; 95% CI: 0.95-1.46, P=0.14, respectively). Subgroup analysis of patients with limited and extensive disease did not show reduced mortality by enoxaparin. The incidence of VTE was significantly reduced in the LMWH arm (HR 0.31; 95% CI: 0.11-0.84, P=0.02). Hemorrhagic events were more frequent in the LMWH-treated group but fatal bleedings occurred in both arms.Conclusion: LMWH enoxaparin in addition to standard therapy did not improve OS in SCLC patients, despite being administered at a supraprophylactic dose and despite resulting in a significant reduction in VTE incidence. Addition of LMWH cannot be generally recommended in the management of SCLC patients, and predictive biomarkers of VTE and LMWH-associated bleeding in cancer patients are warranted. ClinicalTrials.gov: NCT00717938.
AB - Background: Coagulation activation and venous thromboembolism (VTE) are hallmarks of malignant disease and represent a major cause of morbidity and mortality in cancer. Coagulation inhibition with low molecular weight heparin (LMWH) may improve survival specifically in small cell lung cancer (SCLC) patients by preventing VTE and tumor progression; however, randomized trials with well-defined patient populations are needed to obtain conclusive data. The aim of RASTEN was to investigate the survival effect of LMWH enoxaparin in a homogenous population of SCLC patients.Patients and Methods: We performed a randomized, multicenter, open-label trial to investigate the addition of enoxaparin at a supraprophylactic dose (1 mg/kg) to standard treatment in patients with newly diagnosed SCLC. The primary outcome was overall survival (OS), and secondary outcomes were progression-free survival (PFS), incidence of VTE and hemorrhagic events.Results: In RASTEN, 390 patients were randomized over an 8-year period (2008-2016), of which 186 and 191 were included in the final analysis in the LMWH and control arm, respectively. We found no evidence of a difference in OS or PFS by the addition of enoxaparin (HR 1.11; 95% CI: 0.89-1.38, P=0.36 and HR 1.18; 95% CI: 0.95-1.46, P=0.14, respectively). Subgroup analysis of patients with limited and extensive disease did not show reduced mortality by enoxaparin. The incidence of VTE was significantly reduced in the LMWH arm (HR 0.31; 95% CI: 0.11-0.84, P=0.02). Hemorrhagic events were more frequent in the LMWH-treated group but fatal bleedings occurred in both arms.Conclusion: LMWH enoxaparin in addition to standard therapy did not improve OS in SCLC patients, despite being administered at a supraprophylactic dose and despite resulting in a significant reduction in VTE incidence. Addition of LMWH cannot be generally recommended in the management of SCLC patients, and predictive biomarkers of VTE and LMWH-associated bleeding in cancer patients are warranted. ClinicalTrials.gov: NCT00717938.
KW - Journal Article
KW - Coagulation
KW - Enoxaparin
KW - Low-molecular-weight heparin
KW - Randomized phase III trial
KW - Small-cell lung cancer
KW - Venous thromboembolism
UR - http://www.scopus.com/inward/record.url?scp=85042556248&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdx716
DO - 10.1093/annonc/mdx716
M3 - Journal article
C2 - 29106448
SN - 0923-7534
VL - 29
SP - 398
EP - 404
JO - Annals of Oncology
JF - Annals of Oncology
IS - 2
ER -