Thrombotic events in patients with cancer receiving antiangiogenesis agents.
ABSTRACT Tumor-associated neoangiogenesis has recently become a suitable target for antineoplastic drug development. In this overview, we discuss specific drug-associated hemostatic complications, the already known pathogenetic mechanisms involved, and the effect of varying antithrombotic strategies. Multiple agents with angiogenic inhibitory capacity (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib, and sirolimus) have obtained US Food and Drug Administration approval, and many others have entered clinical trials. Arterial and venous thromboembolism and hemorrhage have emerged as significant toxicities associated with the use of angiogenesis inhibitors. We present a detailed analysis of the literature on thrombotic complication of antiangiogenic drugs. Close attention to hemostatic complications during antiangiogenic treatment is warranted. Further studies are required to better understand the pathophysiologic mechanisms involved and to define a safe prophylactic strategy.
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ABSTRACT: Introduction: Kinase inhibitors (KIs) are a class of anticancer drugs that inhibit activity of the enzymes protein kinases, which regulate crucial cellular processes and have a demonstrated role in human oncogenesis. Treatment of advanced forms of endocrine cancer which are not responsive to cytotoxic chemotherapies is challenging and use of KIs is gaining a growing role in this field. Areas covered: The authors summarize the main genetic alterations known to be linked to endocrine tumors, indicating the rationale for utilizing KIs. Furthermore, they present an updated analysis of clinical trials available on PubMed Central, which were pertinent to the activities of KIs in aggressive endocrine cancer. The authors also discuss the adverse effects of KIs and summarize likely involved underlying mechanisms. Expert opinion: KIs are effective in obtaining a radiological disease control and an improvement of progression-free survival in several forms of endocrine cancer but will never deliver a knockout blow of the disease, due to mechanisms of adaptation to circumvent the specific molecular blockade. The new frontier of KIs treatment is to identify agents that could synergize activity of KIs. The true goal will be to perform an overall genotyping of each tumor, thus predicting the impact of combined targeted therapies in the context of a particular constellation of mutant genes.Expert Opinion on Pharmacotherapy 06/2013; 14(9):1187-203. · 2.86 Impact Factor
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ABSTRACT: Angiogenesis affects both wound healing and malignant cell growth through nutrients and oxygen. Vascular endothelial growth factor (VEGF) is the most important element involved in this complex process. Inhibition of VEGF influences angiogenesis and may restrict tumor growth and metastatic ability. Modern anti-angiogenic therapy is based on this theory. Bevacizumab is a recombinant humanized monoclonal antibody (immunoglobulin G1) which binds with VEGF-A forming a large molecule. It can not be bound with VEGF tyrosine kinase receptors preventing VEGF-A incorporation; thus its activity is inhibited inducing blockage of VEGF-mediated angiogenesis. Bevacizumab, in combination with chemotherapy or other novel targeted therapeutic agents, is currently used more frequently in clinical practice, mainly for managing advanced colorectal cancer. It is also used for managing other malignancies, such as breast cancer, pancreatic cancer, prostate cancer, non small-cell lung cancer, metastatic renal carcinoma and ovarian tumors. Although it is generally considered a safe treatment, there are reports of some rare side effects which should be taken into account. Recent experiments in rats and mice show promising results with a wider therapeutic range.World Journal of Gastroenterology 08/2013; 19(31):5051-60. · 2.55 Impact Factor
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ABSTRACT: In this cohort study, the rates of pulmonary embolism (PE), myocardial infarction (MI), and ischemic stroke (IS) before and after lung cancer (LC) diagnosis were compared to cancer-free controls. Patients with LC during 2000-2007 were selected from PALGA, the Dutch Pathology Registry, and linked to the PHARMO medical record linkage system, including drug use and hospitalizations of 3 million inhabitants in the Netherlands. Included LC patients were matched 1:10 by age and gender to cancer-free controls. Hospitalizations for PE, MI, and IS were assessed in the 12 months before and after LC diagnosis. LC patients (N = 3,717) were six times more likely than cancer-free controls to have had a PE in the 12 months before diagnosis. After LC diagnosis, patients experienced an extremely increased risk of PE in the first 6 months (hazard ratio [HR] 16.8; 95 % confidence interval [CI] 7.6-36.8) compared with controls), which decreased to a five times increased risk (HR 5.1; 95 % CI 2.7-9.4) thereafter. However, there were less than two events per 100 person years during both time periods. LC patients receiving chemotherapy were eight times more likely to develop PE, whereas surgery increased the risk on PE three times. For MI and IS, no significant difference was observed compared with cancer-free controls before or after LC diagnosis. LC patients have a higher risk of developing PE compared with cancer-free controls, although the frequency of PE hospitalizations was low. Surgery and chemotherapy were associated with an increased risk of PE.Beiträge zur Klinik der Tuberkulose 06/2013; · 2.06 Impact Factor