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

Safety Profile and Effectiveness of Rivaroxaban for Patients With Venous Thromboembolism in Japan　- Results From Post-Marketing Surveillance (XASSENT)

Circ J. 2023 May 27. doi: 10.1253/circj.CJ-23-0104. Online ahead of print.

ABSTRACT

BACKGROUND: The incidence of venous thromboembolism (VTE; pulmonary embolism [PE] and/or deep vein thrombosis [DVT]) in Japan is increasing, but relatively small numbers of patients from Japan have been included in studies investigating rivaroxaban (a direct factor Xa inhibitor) for the treatment of VTE and preventing its recurrence.Methods and Results: An open-label, prospective, observational study (XASSENT [NCT02558465]) investigated the safety profile and effectiveness of rivaroxaban for ≤2 years in the treatment of VTE and prevention of its recurrence in Japanese clinical practice. Primary outcomes were major bleeding and symptomatic recurrent VTE. Statistical analyses were exploratory and descriptive. Overall, 2,540 patients were enrolled (safety analysis population [SAP], n=2,387; effectiveness analysis population [EAP], n=2,386). In the SAP, >80% of patients received the approved rivaroxaban dose, the mean (standard deviation) age was 66.6 (15.0) years, ≈74% were >50 kg, and 43% had a creatinine clearance ≥80 mL/min. PE+DVT, PE only, and DVT only were reported in 42%, 8%, and 50% of patients, respectively, and active cancer in 17% of patients. Major bleeding was reported in 69 patients (2.89%; 3.60%/patient-year; SAP) and symptomatic PE/DVT recurrence in 26 patients (1.09%; 1.36%/patient-year; EAP) during the treatment period.

CONCLUSIONS: XASSENT provided information on the expected proportions of bleeding and VTE recurrence during rivaroxaban treatment in Japanese clinical practice; no new concerns of safety or effectiveness were found.

PMID:37245989 | DOI:10.1253/circj.CJ-23-0104

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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.

ABSTRACT

Introduction:Glioblastoma (GBM) patients have a 20-30 incidence of venous thromboembolic events. EGFR is a widely used prognostic marker for many cancers. Recent lung cancer studies have described relationships between EGFR amplification and an increased incidence of thromboembolic complications. We aim to explore this relationship in glioblastoma patients. Methods: Two hundred ninety-three consecutive patients with IDH wild-type GBM were included in the analysis. The amplification status of EGFR was measured using fluorescence in situ hybridization (FISH). Centromere 7 (CEP7) expression was recorded to calculate the EGFR-to-CEP7 ratio. All data were collected retrospectively through chart review. Molecular data were obtained through the surgical pathology report at the time of biopsy. Results:There were 112 subjects who were EGFR-amplified (38.2%) and 181 who were non-amplified (61.8%). EGFR amplification status was not significantly correlated with VTE risk overall (p = 0.2001). There was no statistically significant association between VTE and EGFR status after controlling for Bevacizumab therapy (p = 0.1626). EGFR non-amplified status was associated with an increased VTE risk in subjects greater than 60 years of age (p = 0.048). Conclusions:There was no significant difference in occurrence of VTE in patients with glioblastoma, regardless of EGFR amplification status. Patients older than 60 years of age with EGFR amplification experienced a lower rate of VTE, contrary to some reports on non-small-cell lung cancer linking EGFR amplification to VTE risk.

PMID:37232831 | PMC:PMC10217574 | DOI:10.3390/curroncol30050373

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PubMed articles on: Cancer & VTE/PE

Preoperative Venous Thromboembolism Screening and Postoperative Selective Anticoagulant Therapy Effectively Prevents Postoperative Symptomatic Venous Thromboembolism in Gynecological Malignancies: A 15-Year, Single-Center Study

Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231178300. doi: 10.1177/10760296231178300.

ABSTRACT

The aim of this study was to determine which type of prophylaxis was effective for postoperative symptomatic venous thromboembolism (VTE) in patients with gynecological malignancies. A total of 1756 consecutive patients undergoing laparotomy as first-line treatment were included. In Period 1 (2004-2009), low-molecular weight heparin (LMWH) was not available for postoperative VTE prophylaxis, but available in after Period 2 (2009-2013). In Period 3 (2013-2020), patients with pretreatment VTE could switch from LMWH to direct oral anticoagulant (DOAC) as of 2015. Preoperative VTE was screened by measuring D-dimer, followed by venous ultrasound imaging, and computed tomography and/or perfusion lung scintigraphy. Postoperative symptomatic VTE occurred with an incidence of 2.8% by the measures without prophylactic LMWH administration in Period 1. The incidence of postoperative symptomatic VTE was 0.6% in Period 2 and 0.3% in Period 3, being significantly reduced compared with Period 1 (P < .01 and < .0001). The incidences were not significantly different between Periods 2 and 3, but no patient switching to DOAC in Period 3 (n = 79) developed symptomatic VTE. Our preoperative VTE screening and postoperative selective LMWH administration were significantly preventive against postoperative symptomatic VTE.

PMID:37231620 | PMC:PMC10226033 | DOI:10.1177/10760296231178300

31 May 2023

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PubMed articles on: Cardio-Oncology

Quantitative cardiovascular magnetic resonance findings and clinical risk factors predict cardiovascular outcomes in breast cancer patients

PLoS One. 2023 May 30;18(5):e0286364. doi: 10.1371/journal.pone.0286364. eCollection 2023.

ABSTRACT

BACKGROUND: Cardiac magnetic resonance (CMR) global longitudinal strain and circumferential strain abnormalities have been associated with left ventricular ejection fraction (LVEF) reduction and cardiotoxicity from oncologic therapy. However, few studies have evaluated the associations of strain and cardiovascular outcomes.

OBJECTIVES: To assess CMR circumferential and global longitudinal strain (GLS) correlations with cardiovascular outcomes including myocardial infarction, systolic dysfunction, diastolic dysfunction, arrhythmias and valvular disease in breast cancer patients treated with and without anthracyclines and/or trastuzumab therapy.

METHODS: Breast cancer patients with a CMR from 2013-2017 at Yale New Haven Hospital were included. Patient co-morbidities, medications, and cardiovascular outcomes were obtained from chart review. Biostatistical analyses, including Pearson correlations, competing risk regression model, and competing risk survival curves comparing the two groups were analyzed.

RESULTS: 116 breast cancer with CMRs were included in our analysis to assess differences between Anthracycline/Trastuzumab (AT) (62) treated versus non anthracycline/trastuzumab (NAT) (54) treated patients in terms of imaging characteristics and outcomes. More AT patients 17 (27.4%) developed systolic heart failure compared to the NAT group 6 (10.9%), p = 0.025. Statin use was associated with a significant reduction in future arrhythmias (HR 0.416; 95% CI 0.229-0.755, p = 0.004). In a sub-group of 13 patients that underwent stress CMR, we did not find evidence of microvascular dysfunction by sub-endocardial/sub-epicardial myocardial perfusion index ratio after adjusting for ischemic heart disease.

CONCLUSIONS: In our study, CMR detected signs of subclinical cardiotoxicity such as strain abnormalities despite normal LV function and abnormal circumferential strain was associated with adverse cardiovascular outcomes such as valvular disease and systolic heart failure. Thus, CMR is an important tool during and after cancer treatment to identity and prognosticate cancer treatment-related cardiotoxicity.

PMID:37252927 | DOI:10.1371/journal.pone.0286364

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PubMed articles on: Cardio-Oncology

Cardiotoxicities of Non-Chemotherapeutic Metastatic Breast Cancer Treatments

Curr Oncol Rep. 2023 May 30. doi: 10.1007/s11912-023-01427-z. Online ahead of print.