Anti-coagulant Treatment of Cancer-Associated Thrombosis in Frail Patients - Impact of Frailties on the Management of Drug–Drug Interactions

Sep 28, 2026

Uploaded by Mabel

Low-molecular-weight heparins and anti-Xa direct oral anticoagulants are recommended for long-term treatment of cancer-associated thrombosis, yet extensive drug–drug interactions with chemotherapy can alter circulating anticoagulant levels and raise concerns about bleeding or thrombotic recurrence. Improved cancer therapies increase survival and the number of frail patients, but frailties are often excluded from major trials, limiting guideline applicability. A review identifies age, comorbidities and co-medications as key frailty factors, proposes a case-by-case risk assessment and a therapeutic decision algorithm, and highlights coordinated oncology and pharmacy collaboration while calling for further clinical studies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Abstract

Introduction

Cancer risk and thrombotic/bleeding burden

Guideline recommendations for anti-Xa DOACs

Key Points

Frailty and drug–drug interactions

Therapeutic decision algorithm

Multidisciplinary collaboration

Drug–drug interaction mechanisms

CYP3A4/5 and P-gp pathways

Clinical Pharmacokinetics (2023) 62:1523–1531 [https://doi.org/10.1007/s40262-023-01298-4](https://doi.org/10.1007/s40262-023-01298-4) Anti‑coagulant Treatment of Cancer‑Associated Thrombosis in Frail Patients: Impact of Frailties on the Management of Drug–Drug Interactions Claire Grange1 · Catherine Rioufol2 · Pierre‑Jean Souquet3 · Souad Assaad4 Accepted: 10 August 2023 / Published online: 12 October 2023 © The Author(s) 2023 Abstract Low molecular weight heparins (LMWH) and anti-Xa direct oral anti-coagulants (DOACs) are recommended for the longterm treatment of cancer-associated thrombosis (CAT) based on well-documented randomised controlled trials. Anti-Xa DOACs are viewed as a first choice for the treatment of patients with CAT. A large number of drug–drug interactions have been reported between DOACs and chemotherapy drugs, modifying circulating levels of DOAC leading to fears of increased bleeding risks or thrombotic recurrence. Progresses in anti-neoplastic therapies have improved the prognosis and the survival, thus increasing the prevalence of frail patients with cancer. However, since frailties tend to be excluded from large trials due to multiple co-morbidities, current guidelines are not fully applicable to this population. The management of these frail patients with CAT is particularly complex and requires a risk assessment on a case-by-case basis with specific focus on cancer, patient-related risk factors and drug–drug interactions. In this brief review we have identified age, co-morbidities and co-medications as key factors of frailty that require careful attention and we have developed a therapeutic decision algorithm to help clinicians optimising the use of anti-coagulants in patients with cancer with CAT, especially in case of anti-Xa DOACs concomitant medications. With the evaluation of the bleeding risk according to the type of cancer, and anticipating drug–drug interactions intensity, taking into account patient frailties allows the optimisation of the anti-coagulant choice. A systematic collaboration between oncologists, vascular pathology specialists and pharmacists is warranted to ensure an optimal patient management. Clinical studies are needed to determine the real impact of these interactions. 1 Introduction Recent major therapeutic advances have led to an increase in the overall survival of patients with cancer. Population risk factors (e.g. elderly, smoking in women) are associated with an increase in the incidence of cancers. Also, anti-cancer drugs are used for longer treatment periods, resulting in a sharp increase in the prevalence of patients with cancer receiving anti-neoplastic treatments [1 , 2] . The thrombotic risk in patients treated for cancer is increased seven-fold compared with the cancer-free population [3], while the bleeding risk is multiplied by two to three times [4] . Venous thromboembolic (VTE) disease represents the second leading cause of death after neoplastic progression [5] . The individual risk of VTE recurrence or bleeding must be assessed specifically for each patient to support the choice of anti-coagulation. Extended author information available on the last page of the article The 2019 American Society of Clinical Oncology (ASCO) [6] and 2022 International Initiative on Thrombosis and Cancer (ITAC) [7] guidelines recommend anti-Xa direct oral anti-coagulants (DOACs), including rivaroxaban, apixaban and edoxaban, for the treatment of cancer-associated thrombosis (CAT) in patients treated with systemic anti-cancer therapy, without bleeding risk and in the absence of drug–drug interactions with the anticancer treatment, or other concomitant therapy. DOACs are factor Xa inhibitors and/or factor IIa inhibitors. Caution is recommended in patients with gastrointestinal cancers, especially in unresected intra-luminal tumour and in genitourinary tumours, due to the high risk of bleeding observed with anti-Xa DOACs. Anti-Xa DOACs are not indicated in seve

FAQs

Why are drug–drug interactions a major concern in frail patients with cancer-associated thrombosis?

DOAC levels can be modified by interactions with chemotherapy drugs, increasing the risk of bleeding or thrombotic recurrence. In frail patients, reduced drug elimination can further worsen these clinically relevant interactions.

What patient factors are identified as key drivers of frailty in managing CAT?

Age, comorbidities, and co-medications are identified as core factors. These elements help determine the risk of interactions and support anticoagulant selection.

What does the article propose to support clinicians when choosing anticoagulation for CAT?

It proposes a therapeutic decision algorithm based on patient frailties and case-by-case risk assessment, with specific attention to anti-Xa DOACs and concomitant medications.

Sep 28, 2026

Uploaded by Mabel