ABSTRACT

(1) Background: Cancer treatment, including chemotherapy, endocrine therapy, targeted therapy and radiotherapy, has been identified as an important independent risk factor for venous thromboembolism in cancer patients. The aim of the study was to evaluate the effect of adjuvant therapy on the coagulation and fibrinolysis components in invasive breast cancer. (2) Methods: Tissue factor pathway inhibitor (TFPI), tissue factor (TF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) antigen (concentration) and TFPI and TF activities were examined in the blood samples of 60 breast cancer patients treated by adjuvant chemotherapy, endocrine therapy, radiotherapy and immunotherapy. Blood samples were taken 24 h before primary surgery and 8 months after tumour removal surgery. (3) Results: Adjuvant therapy administrated to breast cancer patients significantly increased the concentration of plasma TF, the PAI-1 antigen and also the activity of TFPI and TF, but significantly decreased the level of the t-PA antigen. Combined chemotherapy and endocrine therapy, but not monotherapy, has an important effect on haemostatic biomarker levels. (4) Conclusions: Breast cancer patients receiving adjuvant therapy have an elevated risk of developing a hypercoagulability and hypofibrinolysis state leading to venous thromboembolism.

PMID:37240751 | PMC:PMC10222121 | DOI:10.3390/life13051106

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PubMed articles on: Cancer & VTE/PE

Phase 1 study of GSK3368715, a type I PRMT inhibitor, in patients with advanced solid tumors

Br J Cancer. 2023 May 26. doi: 10.1038/s41416-023-02276-0. Online ahead of print.

ABSTRACT

BACKGROUND: GSK3368715, a first-in-class, reversible inhibitor of type I protein methyltransferases (PRMTs) demonstrated anticancer activity in preclinical studies. This Phase 1 study (NCT03666988) evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of GSK3368715 in adults with advanced-stage solid tumors.

METHODS: In part 1, escalating doses of oral once-daily GSK3368715 (50, 100, and 200 mg) were evaluated. Enrollment was paused at 200 mg following a higher-than-expected incidence of thromboembolic events (TEEs) among the first 19 participants, resuming under a protocol amendment starting at 100 mg. Part 2 (to evaluate preliminary efficacy) was not initiated.

RESULTS: Dose-limiting toxicities were reported in 3/12 (25%) patients at 200 mg. Nine of 31 (29%) patients across dose groups experienced 12 TEEs (8 grade 3 events and 1 grade 5 pulmonary embolism). Best response achieved was stable disease, occurring in 9/31 (29%) patients. Following single and repeat dosing, GSK3368715 maximum plasma concentration was reached within 1 h post dosing. Target engagement was observed in the blood, but was modest and variable in tumor biopsies at 100 mg.

CONCLUSION: Based on higher-than-expected incidence of TEEs, limited target engagement at lower doses, and lack of observed clinical efficacy, a risk/benefit analysis led to early study termination.

TRIAL REGISTRATION NUMBER: NCT03666988.

PMID:37237172 | DOI:10.1038/s41416-023-02276-0

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PubMed articles on: Cancer & VTE/PE

Evaluation of Patient Characteristics Linked to Major Bleeding Events in Patients Prescribed Direct Oral Anticoagulants

Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231172765. doi: 10.1177/10760296231172765.

ABSTRACT

INTRODUCTION: Direct oral anticoagulants (DOACs) demonstrated similar efficacy and lower risk of intracranial hemorrhage than warfarin in patients with atrial fibrillation and venous thromboembolism. Given the lack of data identifying risk factors in patients who bled while on a DOAC, we sought to investigate these characteristics.

MATERIALS AND METHODS: This retrospective chart review was approved by the Mass General Brigham Institutional Review Board and assessed patients who experienced bleeding events while on DOAC therapy from 6/1/2015 to 7/1/2020. Patient characteristics were evaluated, including age, sex, body mass index (BMI), renal function, concomitant therapies, and baseline comorbidities.

RESULTS: Eighty-seven patients were included for analysis, with a median age of 75.8 years. Most patients were female (51.7%) and 24 (27.6%) had a BMI >30. At time-of-event, 21 patients (24.1%) had acute kidney injury. Thirty-three patients (37.9%) were on concomitant antiplatelet therapy (APT), with 31 (35.6%) on single APT and 2 on dual APT. Pertinent comorbidities included hypertension (74.7%), ischemic cerebrovascular accident (28.7%), thyroid abnormality (23.0%), active cancer (14.9%), and anemia (13.8%). Eleven patients (12.6%) had a prior bleeding event. Most patients were on apixaban (69.0%) for the indication of stroke prevention in nonvalvular atrial fibrillation/flutter (72.4%). FDA-approved dosing was used in most patients (92.0%), and all deviations reflected underdosing. Most bleeding events were defined as major (95.4%), occurred at a critical organ site (72.4%), and developed spontaneously (58.6%).

CONCLUSIONS: These data provide insight into characteristics of patients who experience bleeding events while on DOAC therapy. Understanding these potential risk factors may optimize the safe use of these agents.

PMID:37246422 | DOI:10.1177/10760296231172765

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PubMed articles on: Cancer & VTE/PE

The Role of EGFR Amplification in Deep Venous Thrombosis Occurrence in IDH Wild-Type Glioblastoma

Curr Oncol. 2023 May 12;30(5):4946-4956. doi: 10.3390/curroncol30050373.