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A systematic review on the effects of direct oral anticoagulants on cancer growth and metastasis in animal models.
Thromb Res 2020; 187:18-27TR

Abstract

BACKGROUND

Direct oral anticoagulants (DOACs) are now the first choice thromboprophylaxis in cancer patients who do not have a high risk of bleeding. In addition to the anticoagulant effects, potential anti-tumor effects of DOACs have also been studied in animal cancer models. In this study, we summarize the effects of DOACs on cancer growth and metastasis in animal models through a systematic review with a qualitative analysis.

METHODS

PubMed, EMBASE and Web of Science were systematically searched for original studies that describe animal models of cancer in which one of the experimental groups received DOAC monotherapy, and which reported quantitatively on primary tumor or metastases.

RESULTS

Nine studies - reporting a total of 19 animal experiments - met the inclusion criteria. These 19 experiments included spontaneous cancer (n = 2), carcinogenicity (n = 2), xenograft (n = 7) and syngeneic (n = 8) models, encompassing orthotopic (n = 7), subcutaneous (n = 5), intraperitoneal (n = 1) and intravenous (n = 2) injection of cancer cells and included treatments with the DOACs ximelagatran (n = 4), dabigatran etexilate (n = 6) and/or rivaroxaban (n = 11). DOAC treatment decreased tumor growth at implanted and metastatic site in 18.8% (3/16) and 20.0% (3/15) of the experiments, respectively. Conversely, DOACs increased tumor growth at implanted and metastatic site in 6.3% (1/16) and 20.0% (3/15) of the experiments, respectively.

CONCLUSION

DOAC monotherapy resulted in neoplastic changes in a rat carcinogenicity study, showed a lack of effect in mouse xenograft models, while the effect on cancer growth and metastasis in mouse syngeneic models depended on the timing of DOAC treatment and type of cancer model used.

Authors+Show Affiliations

Dept. of Dermatology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: S.Najidh@lumc.nl.Einthoven Laboratory for Vascular and Regenerative Medicine, Div. of Thrombosis & Hemostasis, Dept. of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: H.H.Versteeg@lumc.nl.Einthoven Laboratory for Vascular and Regenerative Medicine, Div. of Thrombosis & Hemostasis, Dept. of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: J.T.Buijs@lumc.nl.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31945588

Citation

Najidh, Safa, et al. "A Systematic Review On the Effects of Direct Oral Anticoagulants On Cancer Growth and Metastasis in Animal Models." Thrombosis Research, vol. 187, 2020, pp. 18-27.
Najidh S, Versteeg HH, Buijs JT. A systematic review on the effects of direct oral anticoagulants on cancer growth and metastasis in animal models. Thromb Res. 2020;187:18-27.
Najidh, S., Versteeg, H. H., & Buijs, J. T. (2020). A systematic review on the effects of direct oral anticoagulants on cancer growth and metastasis in animal models. Thrombosis Research, 187, pp. 18-27. doi:10.1016/j.thromres.2019.12.022.
Najidh S, Versteeg HH, Buijs JT. A Systematic Review On the Effects of Direct Oral Anticoagulants On Cancer Growth and Metastasis in Animal Models. Thromb Res. 2020 Jan 8;187:18-27. PubMed PMID: 31945588.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A systematic review on the effects of direct oral anticoagulants on cancer growth and metastasis in animal models. AU - Najidh,Safa, AU - Versteeg,Henri H, AU - Buijs,Jeroen T, Y1 - 2020/01/08/ PY - 2019/10/25/received PY - 2019/12/18/revised PY - 2019/12/28/accepted PY - 2020/1/17/pubmed PY - 2020/1/17/medline PY - 2020/1/17/entrez KW - Anticoagulants KW - Dabigatran KW - Direct thrombin inhibitors KW - Models, animal KW - Neoplasms, experimental KW - Rivaroxaban SP - 18 EP - 27 JF - Thrombosis research JO - Thromb. Res. VL - 187 N2 - BACKGROUND: Direct oral anticoagulants (DOACs) are now the first choice thromboprophylaxis in cancer patients who do not have a high risk of bleeding. In addition to the anticoagulant effects, potential anti-tumor effects of DOACs have also been studied in animal cancer models. In this study, we summarize the effects of DOACs on cancer growth and metastasis in animal models through a systematic review with a qualitative analysis. METHODS: PubMed, EMBASE and Web of Science were systematically searched for original studies that describe animal models of cancer in which one of the experimental groups received DOAC monotherapy, and which reported quantitatively on primary tumor or metastases. RESULTS: Nine studies - reporting a total of 19 animal experiments - met the inclusion criteria. These 19 experiments included spontaneous cancer (n = 2), carcinogenicity (n = 2), xenograft (n = 7) and syngeneic (n = 8) models, encompassing orthotopic (n = 7), subcutaneous (n = 5), intraperitoneal (n = 1) and intravenous (n = 2) injection of cancer cells and included treatments with the DOACs ximelagatran (n = 4), dabigatran etexilate (n = 6) and/or rivaroxaban (n = 11). DOAC treatment decreased tumor growth at implanted and metastatic site in 18.8% (3/16) and 20.0% (3/15) of the experiments, respectively. Conversely, DOACs increased tumor growth at implanted and metastatic site in 6.3% (1/16) and 20.0% (3/15) of the experiments, respectively. CONCLUSION: DOAC monotherapy resulted in neoplastic changes in a rat carcinogenicity study, showed a lack of effect in mouse xenograft models, while the effect on cancer growth and metastasis in mouse syngeneic models depended on the timing of DOAC treatment and type of cancer model used. SN - 1879-2472 UR - https://www.unboundmedicine.com/medline/citation/31945588/A_systematic_review_on_the_effects_of_direct_oral_anticoagulants_on_cancer_growth_and_metastasis_in_animal_models L2 - https://linkinghub.elsevier.com/retrieve/pii/S0049-3848(19)30555-9 DB - PRIME DP - Unbound Medicine ER -