A systematic review on the effects of direct oral anticoagulants on cancer growth and metastasis in animal models

Najidh, S. and Versteeg, H. H. and Buijs, J. T.

Thromb Res (2020) 187: 18–27

DOI: 10.1016/j.thromres.2019.12.022

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.

Citation

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. Thromb Res, 187, 18–27. https://doi.org/10.1016/j.thromres.2019.12.022 *Anticoagulants, *Dabigatran, *Direct thrombin inhibitors, *Models, animal, *Neoplasms, experimental, *Rivaroxaban

Keywords

• *Anticoagulants
• *Dabigatran
• *Direct thrombin inhibitors
• *Models
• animal
• *Neoplasms
• experimental
• *Rivaroxaban