Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current evidence

García-Escobar, Ignacio; Brozos-Vázquez, Elena; Abad, David Gutiérrez; Martínez‐Marín, Virginia; Pachón, Vanessa; Martín, Andrés J. Muñoz

doi:10.1007/s12094-020-02506-4

Cited by 3 publications

(3 citation statements)

References 94 publications

(91 reference statements)

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“…This can in turn support the growth and progression of tumors [ 28 , 29 , 30 ]. Oral anticoagulants are used to avoid such consequences because venous thromboembolic illness is a frequent cause of death in cancer patients [ 30 , 31 , 32 ]. Proliferative cancer cells, platelets, and red blood cells can be detected in venous thrombosis with advanced RCC [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical significance, molecular characterization, and immune microenvironment analysis of coagulation‐related genes in clear cell renal cell carcinoma

Chen,

Zhao,

et al. 2024

Cancer Innovation

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BackgroundNumerous studies have revealed a tight connection between tumor development and the coagulation system. However, the effects of coagulation on the prognosis and tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) remain poorly understood.MethodsWe employed the consensus clustering method to characterize distinct molecular subtypes associated with coagulation patterns. Subsequently, we examined variations in the overall survival (OS), genomic profiles, and TME characteristics between these subtypes. To develop a prognostic coagulation‐related risk score (CRRS) model, we utilized the least absolute shrinkage and selection operator Cox regression and stepwise multivariate Cox regression analyses. We also created a nomogram to aid in the clinical application of the risk score, evaluating the relationships between the CRRS and the immune microenvironment, responsiveness to immunotherapy, and targeted treatment. The clinical significance of PLAUR and its biological function in ccRCC were also further analyzed.ResultsThere were significant differences in clinical features, prognostic stratification, genomic variation, and TME characteristics between the two coagulation‐related subtypes. We established and validated a CRRS using six coagulation‐related genes that can be employed as an effective indicator of risk stratification and prognosis estimation for ccRCC patients. Significant variations in survival outcomes were observed between the high‐ and low‐risk groups. The nomogram was proficient in predicting the 1‐, 3‐, and 5‐year OS. Additionally, the CRRS emerged as a novel tool for evaluating the clinical effectiveness of immunotherapy and targeted treatments in ccRCC. Moreover, we confirmed upregulated PLAUR expression in ccRCC samples that was significantly correlated with poor patient prognosis. PLAUR knockdown notably inhibited ccRCC cell proliferation and migration.ConclusionOur data suggested that CRRS may be employed as a reliable predictive biomarker that can provide therapeutic benefits for immunotherapy and targeted therapy in ccRCC.

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Section: Discussionmentioning

confidence: 99%

Clinical significance, molecular characterization, and immune microenvironment analysis of coagulation‐related genes in clear cell renal cell carcinoma

Chen,

Zhao,

et al. 2024

Cancer Innovation

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“…Tumor can be affected by the production of procoagulant factors, including tissue factor (TF), cancer procoagulant proteins, microparticles (MPs), proangiogenic factors, and cytokines, etc. The production and activation of these procoagulant factors further promote tumorigenesis and development, resulting in a chronic hypercoagulable state and an increased incidence of thrombotic events ( 32 ). It has been found that elevated plasma fibrinogen in SKCM patients is often associated with decreased survival ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Characterization of coagulation-related gene signature to predict prognosis and tumor immune microenvironment in skin cutaneous melanoma

et al. 2022

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BackgroudSkin cutaneous melanoma (SKCM) is an extremely metastatic form of skin cancer. However, there are few valuable molecular biomarkers, and accurate diagnosis is still a challenge. Hypercoagulable state encourages the infiltration and development of tumor cells and is significantly associated with poor prognosis in cancer patients. However, the use of a coagulation-related gene (CRG) signature for prognosis in SKCM, on the other hand, has yet to be determined.MethodWe used data from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases to identify differentially expressed CRGs, then designed a prognostic model by using the LASSO algorithm, univariate and multivariate Cox regression analysis, and constructed a nomogram which was evaluated by calibration curves. Moreover, the Gene Expression Omnibus (GEO), GSE54467 was used as an independent validation. The correlation between risk score and clinicopathological characteristics, tumor microenvironment (TME), and immunotherapy was further analyzed.ResultsTo develop a prognostic model, seven CRGs in SKCM patients related to overall survival (OS) were selected: ANG, C1QA, CFB, DUSP6, KLKB1, MMP7, and RABIF. According to the Kaplan-Meier survival analysis, an increased OS was observed in the low-risk group than in the high-risk group (P<0.05). Immunotherapy was much more beneficial in the low-risk group, as per immune infiltration, functional enrichment, and immunotherapy analysis.ConclusionsThe prognosis of SKCM patients may now be predicted with the use of a CRG prognostic model, thus guiding the development of treatment plans for SKCM patients and promoting OS rates.

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“…Venous thromboembolisms (VTEs) are a common and clinically significant complication in cancer patients, contributing to their mortality and morbidity ( Garcia-Escobar et al, 2021 ). Compared to non-cancer-related VTEs, cancer-related VTEs cause a higher risk of recurrent VTEs and major bleeding ( Vedovati et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban

Wang,

Li,

et al. 2023

Front. Pharmacol.

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Background: Almonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is commonly used as a first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations. Rivaroxaban and apixaban are a selective, direct factor Xa inhibitor used to treat venous thromboembolism (VTE), which is a frequent complication of NSCLC. Rivaroxaban and apixaban are substrates of CYP3A4, P-gp and BCRP, whereas almonertinib is an inhibitor of P-gp and BCRP. Rivaroxaban or apixaban are often prescribed together with almonertinib in NSCLC patients, but clear information on pharmacokinetic drug interaction is lacking. Therefore, this study aimed to unravel the extent of interactions between almonertinib-rivaroxaban and almonertinib apixaban in rats, and whether the pharmacokinetic interaction can be mitigated by rivaroxaban and apixaban dose adjustment.Methods: Rats were divided into ten groups (n = 6) that received rivaroxaban (2 mg/kg) (group 1), apixaban (0.5 mg/kg) (group 2), almonertinib (15 mg/kg) (group 3, group 4), almonertinib with rivaroxaban (2 mg/kg) (group 5), almonertinib with rivaroxaban (1 mg/kg) (group 6), almonertinib with apixaban (0.5 mg/kg) (group 7), almonertinib with apixaban (0.25 mg/kg) (group 8), rivaroxaban (2 mg/kg) with almonertinib (group 9), apixaban (0.5 mg/kg) with almonertinib (group 10). The concentrations of drugs were determined by an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The levels of messenger RNA were determined using quantitative real-time polymerase chain reaction (qRT-PCR).Results and Discussion: The results indicate that almonertinib increased the Cmax and AUC0-t of 2 mg/kg rivaroxaban by 3.30 and 3.60-fold, 1 mg/kg rivaroxaban by 1.28 and 1.90-fold. Almonertinib increased the Cmax and AUC0-t of 0.5 mg/kg apixaban by 2.69 and 2.87-fold, 0.25 mg/kg apixaban by 2.19 and 2.06-fold. In addition, rivaroxaban also increased systemic exposure to almonertinib. The results of qRT-PCR showed that almonertinib reduced the expression of Cyp3a1 in liver and intestine, and Abcb1a, Abcg2 in intestine and kidney. The pharmacokinetic results suggest that it is important to take special care of the interactions of these drugs in clinical applications.

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Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current evidence

Cited by 3 publications

References 94 publications

Clinical significance, molecular characterization, and immune microenvironment analysis of coagulation‐related genes in clear cell renal cell carcinoma

Clinical significance, molecular characterization, and immune microenvironment analysis of coagulation‐related genes in clear cell renal cell carcinoma

Characterization of coagulation-related gene signature to predict prognosis and tumor immune microenvironment in skin cutaneous melanoma

In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban

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