Abstract Cancer-associated thrombosis (CAT) remains a major cause of morbidity and mortality in patients with malignancy. Direct oral anticoagulants (DOACs) have expanded the therapeutic armamentarium for CAT and are now widely used as alternatives to low molecular weight heparins (LMWHs). However, the increasing complexity of contemporary oncologic care has heightened concerns regarding clinically relevant drug–drug interactions (DDIs). All DOACs are substrates of P-glycoprotein, and some undergo partial metabolism via cytochrome P4503A4, rendering them more susceptible to pharmacokinetic (PK) modulation by anticancer agents. Moreover, several antineoplastic drugs exert intrinsic prothrombotic or hemorrhagic effects, thereby introducing pharmacodynamic interactions that may further destabilize the already dysregulated hemostatic system in cancer. Despite these theoretical concerns, evidence from randomized trials and real-world studies remains limited and largely derived from subgroup analyses, PK investigations in healthy volunteers, or retrospective registries. Consequently, the true clinical magnitude of DDIs in CAT remains incompletely defined. This review critically appraises the pharmacological basis, clinical evidence, and translational implications of DDIs between DOACs and anticancer therapies. We propose that DDIs in CAT should not be viewed solely as PK phenomena, but also as potential biological amplifiers of cancer-associated coagulopathy. Until prospective, dedicated studies become available, a structured/individualized approach—integrating thrombotic/bleeding risk, interacting medications, and patient-specific factors—is warranted.
Tufano et al. (Tue,) studied this question.
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