The changing landscape of anticoagulation in cancer-associated thrombosis.
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ABSTRACT:
SUBMITTER: Lee AYY
PROVIDER: S-EPMC7065483 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
Publications
The changing landscape of anticoagulation in cancer-associated thrombosis.
Blood advances 20200301 5
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Project description:BackgroundThe management of anticoagulation for cancer-associated thrombosis (CAT) in patients with thrombocytopenia is controversial. Whereas some studies suggest that administration of reduced-dose low-molecular-weight heparin (LMWH) or temporary discontinuation for moderate and severe thrombocytopenia may be a safe and effective, others suggest full-dose anticoagulation with transfusion support. We sought to address this important knowledge gap and summarize the literature comparing these two common management strategies.MethodsA systematic review of the literature (PROSPERO CRD42017077127) using MEDLINE (inception to September 2017) was conducted. We included studies that reported recurrent venous thromboembolism (VTE) and major bleeding complications among patients treated with both of the two most common management strategies: therapeutic anticoagulation with platelet transfusion support and dose-modified anticoagulation for periods when the platelet count is <50 × 109/L.ResultsA total of 134 article records were identified on the initial search and 10 articles underwent full text review. Two observational studies met the inclusions criteria. A total of 121 patients with CAT and thrombocytopenia were included. Forty-two of these patients had pulmonary embolism and 87 had deep vein thrombosis (DVT) including 38 upper extremity DVT. Overall, 27% of patients, regardless of their treatment strategy, experienced recurrent VTE. Thirteen percent of anticoagulated patients (15% of all patients) experienced a major bleeding episode. Meta-analysis could not be conducted.ConclusionsOur findings do not support one management strategy over another to treat CAT patients with thrombocytopenia. However, the data highlights the heightened risk of recurrent VTE in this patient population despite the thrombocytopenia.
| S-EPMC6178713 | biostudies-literature
Project description:Pharmacogenomics in oncology holds the promise to personalize cancer therapy. However, its clinical application is still limited to a few genes, and, in the large majority of cancers, the correlation between genotype and clinical outcome has been disappointing. One possible explanation is that current pharmacogenomic studies do not take into account the emerging role of cancer stem cells (CSCs) in drug sensitivity and resistance. CSCs are a subpopulation of cells driven by specific signal-transduction pathways, but genetic variants affecting their activity are generally neglected in current pharmacogenomic studies. Moreover, in several malignancies, CSCs represent a rare sub-population; therefore, whole tumor profiling might mask CSC gene expression patterns. This article reviews current evidence on CSC chemoresistance and shows how common genetic variations in CSC-related genes may predict individual response to anti-cancer agents. Furthermore, we provide insights into the design of pharmacogenomic studies to address the clinical usefulness of CSC genetic profiling.
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Project description:Bladder cancer is the 10th most common cancer type in the world. There were more than 573,000 new cases of bladder cancer in 2020. It is the 13th most common cause of cancer death with an estimated more than 212,000 deaths worldwide. Low-grade non-muscle-invasive bladder cancer (NMIBC) is usually successfully managed with transurethral resection (TUR) and overall survival for NMIBC reaches 90% according to some reports. However, long-term survival for muscle-invasive bladder cancer (MIBC) and metastatic bladder cancer remains low. Treatment options for bladder cancer have undergone a rapid change in recent years. Immune checkpoint inhibitors (ICI), targeted therapies, and antibody-drug conjugates are available now. As bladder cancer is genetically heterogeneous, the optimization of patient selection to identify those most likely to benefit from a specific therapy is an urgent issue in the treatment of patients with bladder cancer.
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Project description:To perform a systematic review and network meta-analysis evaluating the efficacy and safety of low-molecular-weight heparins (LMWHs), vitamin K antagonists (VKAs), and direct-acting oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). We searched MEDLINE, Cochrane Central Register of Controlled Trials, and conference abstracts through March 2018. Randomized controlled trials (RCTs) enrolling adults with CAT comparing 2 or more full-dose anticoagulants (LMWH, VKA, and DOAC) and evaluating recurrent venous thromboembolism (VTE), major bleeding, and/or all-cause mortality were included. Reviewers identified studies, extracted data, and assessed the quality of the evidence in duplicate. A frequentist network meta-analysis, which uses direct and indirect evidence to simultaneously compare multiple interventions, was performed using a random-effects approach. Results are reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). We included 13 RCTs (n = 6292): 7 compared LMWHs with VKAs, 4 compared DOACs with VKAs, and 2 compared DOACs with LMWHs. The risk of recurrent VTE was significantly reduced by 28% and 54% with a DOAC compared to an LMWH and a VKA, respectively. Low-molecular-weight heparins significantly reduced the risk of recurrent VTE by 36% versus VKAs. The risk of major bleeding was 14% higher with DOACs compared to LMWHs and 15% and 25% lower with DOACs and LMWHs versus VKAs, although 95% CIs included unity for each. The risk of all-cause mortality appeared similar for all 3 comparisons (RR = 1.0 for each comparison). Direct-acting oral anticoagulants appeared superior in reducing recurrent VTE in patients with CAT compared to LMWH and VKAs, but an increased risk of major bleeding versus LMWH cannot be ruled out.
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Project description:BackgroundPatients with cancer-associated venous thromboembolism (VTE) are recommended to receive treatment with therapeutic anticoagulation for at least 3-6 months. Little data exist on extended treatment beyond 6 months.ObjectiveTo comprehensively summarize the best available evidence on incidence of recurrent VTE and major bleeding 6-12 months after the index event in patients with cancer-associated VTE.Patients/methodsWe systematically screened biomedical databases (MEDLINE, Embase, CENTRAL) to identify studies reporting recurrent VTE and/or bleeding events between 6 and 12 months after a diagnosis of cancer-associated VTE. Based on the observed heterogeneity in study design, setting, patient cohort characteristics, anticoagulation strategies, and outcome rates, no overall quantitative estimate of outcome rates was calculated.ResultsWe screened 2597 publications and identified 11 eligible studies matching predefined in-/exclusion criteria, reporting on 3019 patients specifically during the 6- to 12-month period post-index VTE. Overall rates of recurrent VTE in this timeframe varied substantially (1%-12%), with the highest risk observed in the patient subgroup with residual vein thrombosis present at 6 months randomized to receive no anticoagulation (13%-15%). Reported rates of major bleeding between 6 and 12 months were between 2% and 5%.ConclusionsIn this systematic review, we provide a comprehensive and structured summary of the best available evidence on recurrence and bleeding risk between 6 and 12 months after cancer-associated VTE. VTE recurrence remains common beyond 6 months and continuation of different anticoagulation strategies has an acceptable safety profile indicated by lower bleeding rates. These findings support guideline recommendations to continue anticoagulation treatment beyond 6 months in patients with active cancer.
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Project description:Despite significant progress, metastatic urothelial cancer remains an incurable condition with a limited life expectancy. Platinum-based chemotherapy is still the mainstay of treatment for metastatic disease, but immunotherapy, antibody drug conjugates, and targeted agents have shown encouraging results in several recent practice changing trials. In this review, we discuss the standard of care, recent therapeutic advances, ongoing clinical trials, and future perspectives in metastatic urothelial carcinoma.
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Project description:The practising clinician treating a patient with metastatic clear cell renal cell carcinoma (CCRCC) faces a difficult task of choosing the most appropriate therapeutic regimen in a rapidly developing field with recommendations derived from clinical trials. NCCN guidelines for kidney cancer initiated a major shift in risk categorization and now include emerging treatments in the neoadjuvant setting. Updates of European Association of Urology clinical guidelines also include immune checkpoint inhibition as the first-line treatment. Randomized trials have demonstrated a survival benefit for ipilimumab and nivolumab combination in the intermediate and poor-risk group, while pembrolizumab plus axitinib combination is recommended not only for unfavorable disease but also for patients who fit the favorable risk category. Currently vascular endothelial growth factor (VEGF) targeted therapy based on tyrosine kinase inhibitors (TKI), sunitinib and pazopanib is the alternative regimen for patients who cannot tolerate immune checkpoint inhibitors (ICI). Cabozantinib remains a valid alternative option for the intermediate and high-risk group. For previously treated patients with TKI with progression, nivolumab, cabozantinib, axitinib, or the combination of ipilimumab and nivolumab appear the most plausible alternatives. For patients previously treated with ICI, any VEGF-targeted therapy, not previously used in combination with ICI therapy, seems to be a valid option, although the strength of this recommendation is weak. The indication for cytoreductive nephrectomy (CN) is also changing. Neoadjuvant systemic therapy does not add perioperative morbidity and can help identify non-responders, avoiding unnecessary surgery. However, the role of CN should be investigated under the light of new immunotherapeutic interventions. Also, markers of response to ICI need to be identified before the optimal selection of therapy could be determined for a particular patient.
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Project description:Despite nearly a century of clinical use as a blood thinner, heparin's rapid serum clearance and potential to induce severe bleeding events continue to urge the development of more effective controlled delivery strategies. Subcutaneous depots that steadily release the anticoagulant into circulation represent a promising approach to reducing overdose frequency, sustaining therapeutic concentrations of heparin in plasma, and prolonging anticoagulant activity in a safe and effective manner. Subcutaneously deliverable heparin-peptide nanogranules that allow for long-lasting heparin bioavailability in the circulatory system, while enabling on-demand activation of heparin's anticoagulant effects in the thrombus microenvironment, are reported. Biophysical studies demonstrate this responsive behavior is due to the sequestration of heparin within self-assembling peptide nanofibrils and its mechanically actuated decoupling to elicit antithrombotic effects at the clotting site. In vivo studies show these unique properties converge to allow subcutaneous nanogranule depots to extend heparin serum concentrations for an order of magnitude longer than standard dosing regimens while enabling prolonged and controlled anticoagulant activity. This biohybrid delivery system demonstrates a potentially scalable platform for the development of safer, easier to administer, and more effective antithrombotic nanotechnologies.
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