Increased bleeding risk associated with concurrent vascular endothelial growth factor receptor tyrosine kinase inhibitors and low‐molecular‐weight heparin

Some cancer patients who are diagnosed with thromboembolism may require dual treatment with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) and factor Xa inhibitors (low‐molecular‐weight heparin [LMWH] or direct oral anticoagulants [DOACs]). However, to the authors' knowledge, the safety of such combinations has not been well characterized.

[1]  A. Torbicki,et al.  Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. , 2020, The New England journal of medicine.

[2]  Y. Lacasse,et al.  DOAC compared to LMWH in the treatment of cancer related-venous thromboembolism: a systematic review and meta-analysis , 2020, Journal of Thrombosis and Thrombolysis.

[3]  G. Raskob,et al.  Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism , 2019, Journal of Vascular Surgery: Venous and Lymphatic Disorders.

[4]  Y. Liu,et al.  Comparison of efficacy and toxicity of bevacizumab, endostar and apatinib in transgenic and human lung cancer xenograftzebrafish model , 2018, Scientific Reports.

[5]  J. Heemskerk,et al.  Acquired platelet antagonism: off‐target antiplatelet effects of malignancy treatment with tyrosine kinase inhibitors , 2018, Journal of thrombosis and haemostasis : JTH.

[6]  G. Lyman,et al.  Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  R. Touyz,et al.  Vascular toxicities with VEGF inhibitor therapies–focus on hypertension and arterial thrombotic events , 2018, Journal of the American Society of Hypertension : JASH.

[8]  E. Voest,et al.  Platelet function is disturbed by the angiogenesis inhibitors sunitinib and sorafenib, but unaffected by bevacizumab , 2018, Angiogenesis.

[9]  G. Zeng,et al.  Crosstalk between VEGFR and other receptor tyrosine kinases for TKI therapy of metastatic renal cell carcinoma , 2018, Cancer Cell International.

[10]  G. Raskob,et al.  Edoxaban for the Treatment of Cancer‐Associated Venous Thromboembolism , 2017, The New England journal of medicine.

[11]  C. Grüllich Cabozantinib: Multi-kinase Inhibitor of MET, AXL, RET, and VEGFR2. , 2018, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[12]  D. Poslinski,et al.  Phase I Study of Dalteparin in Combination With Sunitinib in Patients With Metastatic Clear Cell Renal Carcinoma , 2017, Clinical genitourinary cancer.

[13]  G. Wei,et al.  Risk of venous and arterial thromboembolic events associated with VEGFR-TKIs: a meta-analysis , 2017, Cancer Chemotherapy and Pharmacology.

[14]  T. Choueiri,et al.  Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  Gordon C Jayson,et al.  Antiangiogenic therapy in oncology: current status and future directions , 2016, The Lancet.

[16]  S. Schulman,et al.  Definition of clinically relevant non‐major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non‐surgical patients: communication from the SSC of the ISTH , 2015, Journal of thrombosis and haemostasis : JTH.

[17]  Catch Investigators Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial , 2015 .

[18]  Jianwen Cai,et al.  Modelling recurrent events: a tutorial for analysis in epidemiology. , 2015, International journal of epidemiology.

[19]  A. Khorana,et al.  Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. , 2015, JAMA.

[20]  J. Reeves,et al.  Pazopanib versus sunitinib in metastatic renal-cell carcinoma. , 2013, The New England journal of medicine.

[21]  R. Motzer,et al.  Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial , 2011, The Lancet.

[22]  J. Christensen,et al.  HGF/c-Met acts as an alternative angiogenic pathway in sunitinib-resistant tumors. , 2010, Cancer research.

[23]  T. Choueiri,et al.  Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. , 2009, The Lancet. Oncology.

[24]  M. Hirashima Regulation of endothelial cell differentiation and arterial specification by VEGF and Notch signaling , 2009, Anatomical science international.

[25]  E. Olson,et al.  Control of endothelial cell proliferation and migration by VEGF signaling to histone deacetylase 7 , 2008, Proceedings of the National Academy of Sciences.

[26]  T. Cloughesy,et al.  Safety of anticoagulation use and bevacizumab in patients with glioma. , 2008, Neuro-oncology.

[27]  H. Verheul,et al.  Possible molecular mechanisms involved in the toxicity of angiogenesis inhibition , 2007, Nature Reviews Cancer.

[28]  Hirohisa Yano,et al.  Angiogenesis in Cancer , 2006, Vascular health and risk management.

[29]  S. Schulman,et al.  Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non‐surgical patients , 2005, Journal of thrombosis and haemostasis : JTH.

[30]  M. Prins,et al.  Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. , 2003, The New England journal of medicine.

[31]  V. V. van Hinsbergh,et al.  Analysis of Coagulation Cascade and Endothelial Cell Activation During Inhibition of Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor Pathway in Cancer Patients , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[32]  M. Ishihara,et al.  Structural features in heparin that interact with VEGF165 and modulate its biological activity. , 1999, Glycobiology.