Service Pharmacie, AP-HP, Hôpital Cochin, 75014, Paris, France.
AP-HP, Hôpital Cochin, Service d'oncologie, 75014, Paris, France.
Support Care Cancer. 2024 Sep 10;32(10):648. doi: 10.1007/s00520-024-08829-0.
Concomitant direct oral anticoagulants (DOACs) and tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (anti-VEGF TKI) have been associated with a higher risk of bleeding. Nevertheless, concomitant administration seems frequent in clinical practice in patients with cancer-associated thrombosis and appears to be safe according to the retrospective study by Boileve A. et al. But the risk of an additional pharmacokinetic interaction between anti-VEGF TKI and DOACs must be considered, in case of P-glycoprotein (P-gp) inhibition by the TKI. We describe a case report with a major bleeding event in a renal metastatic cancer patient treated with cabozantinib and rivaroxaban. This case highlights the difficult therapeutic decision in a complex patient with cancer-associated thrombosis, who refused the anticoagulant subcutaneous route. Accumulation of bleeding risk factors (genito-urinary tumor localization) was additive to several pharmacodynamic interactions (acetylsalicylic acid, venlafaxine) and a potential pharmacokinetic interaction between cabozantinib and rivaroxaban. Indeed, cabozantinib-related P-glycoprotein inhibition could have led to a supratherapeutic level of rivaroxaban, contributing partly to the bleeding event. Before combining an anti-VEGF TKI and DOACs, a multidisciplinary pretherapeutic assessment seems crucial to evaluate the patient's bleeding risk factors, pharmacodynamic interactions, and the risk of pharmacokinetic interactions mediated by P-gp.
同时使用直接口服抗凝药物（DOACs）和针对血管内皮生长因子受体的酪氨酸激酶抑制剂（anti-VEGF TKI）与更高的出血风险相关。然而，根据 Boileve A 等人的回顾性研究，在伴有癌症相关血栓形成的患者中，联合用药在临床实践中似乎很常见，而且似乎是安全的。但是，如果 TKI 抑制 P 糖蛋白（P-gp），则必须考虑 anti-VEGF TKI 和 DOACs 之间可能存在的额外药代动力学相互作用的风险。我们描述了一例卡博替尼和利伐沙班治疗肾转移性癌症患者发生大出血事件的病例报告。该病例突出了在伴有癌症相关血栓形成的复杂患者中进行治疗决策的困难，因为该患者拒绝接受抗凝皮下途径。出血风险因素（泌尿生殖系统肿瘤定位）的累积与几种药效学相互作用（乙酰水杨酸、文拉法辛）以及卡博替尼和利伐沙班之间潜在的药代动力学相互作用相加。事实上，卡博替尼相关的 P-gp 抑制可能导致利伐沙班的治疗水平升高，部分导致出血事件的发生。在联合使用 anti-VEGF TKI 和 DOACs 之前，进行多学科的治疗前评估似乎至关重要，以评估患者的出血风险因素、药效学相互作用以及由 P-gp 介导的药代动力学相互作用的风险。
