scholarly journals Cardio-oncology: management of cardiovascular toxicity

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 120
Author(s):  
Timothy M. Markman ◽  
Maurie Markman
Keyword(s):  
Heart Failure ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Management Strategies ◽  
Chemotherapeutic Agents ◽  
Vascular Endothelial ◽  
Cardiovascular Toxicity ◽  
Careful Monitoring ◽  
Vascular Toxicity ◽  
Endothelial Growth Factor

Traditional chemotherapeutic agents and newer targeted therapies for cancer have the potential to cause cardiovascular toxicities. These toxicities can result in arrhythmias, heart failure, vascular toxicity, and even death. It is important for oncologists and cardiologists to understand the basic diagnostic and management strategies to employ when these toxicities occur. While anti-neoplastic therapy occasionally must be discontinued in this setting, it can often be maintained with caution and careful monitoring. In the second of this two-part review series, we focus on the management of cardiovascular toxicity from anthracyclines, HER2/ErbB2 inhibitors, immune checkpoint inhibitors, and vascular endothelial growth factor inhibitors.

scholarly journals Cardio-Oncology: mechanisms of cardiovascular toxicity

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 113 ◽  
Author(s):  
Timothy M. Markman ◽  
Maurie Markman
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Chemotherapeutic Agents ◽  
Vascular Endothelial ◽  
Cardiovascular Toxicity ◽  
Management Of Complications ◽  
Wide Range ◽  
Endothelial Growth Factor

The therapeutic options available to treat a wide range of malignancies are rapidly increasing. At the same time, the population being treated is aging with more cardiovascular risk factors, comorbid conditions, and associated poor cardiac reserve. Both traditional chemotherapeutic agents (for example, anthracyclines) and newer therapies (for example, targeted tyrosine kinase inhibitors and immune checkpoint inhibitors) have demonstrated profound cardiovascular toxicities. It is important to understand the mechanisms of these toxicities to establish strategies for the prevention and management of complications—arrhythmias, heart failure, and even death. In the first of this two-part review series, we focus on what is known and hypothesized about the mechanisms of cardiovascular toxicity from anthracyclines, HER2/ErbB2 inhibitors, immune checkpoint inhibitors, and vascular endothelial growth factor inhibitors.

scholarly journals Updates on Anticancer Therapy-Mediated Vascular Toxicity and New Horizons in Therapeutic Strategies

2021 ◽  
Vol 8 ◽  
Author(s):  
Po-Yen Hsu ◽  
Aynura Mammadova ◽  
Nadia Benkirane-Jessel ◽  
Laurent Désaubry ◽  
Canan G. Nebigil
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Alkylating Agents ◽  
Chemotherapeutic Agents ◽  
Vital Role ◽  
Vascular Endothelial ◽  
Comprehensive Overview ◽  
Vascular Toxicity ◽  
Vasculogenesis And Angiogenesis ◽  
Endothelial Growth Factor

Vascular toxicity is a frequent adverse effect of current anticancer chemotherapies and often results from endothelial dysfunction. Vascular endothelial growth factor inhibitors (VEGFi), anthracyclines, plant alkaloids, alkylating agents, antimetabolites, and radiation therapy evoke vascular toxicity. These anticancer treatments not only affect tumor vascularization in a beneficial manner, they also damage ECs in the heart. Cardiac ECs have a vital role in cardiovascular functions including hemostasis, inflammatory and coagulation responses, vasculogenesis, and angiogenesis. EC damage can be resulted from capturing angiogenic factors, inhibiting EC proliferation, survival and signal transduction, or altering vascular tone. EC dysfunction accounts for the pathogenesis of myocardial infarction, atherothrombosis, microangiopathies, and hypertension. In this review, we provide a comprehensive overview of the effects of chemotherapeutic agents on vascular toxicity leading to hypertension, microvascular rarefaction thrombosis and atherosclerosis, and affecting drug delivery. We also describe the potential therapeutic approaches such as vascular endothelial growth factor (VEGF)-B and prokineticin receptor-1 agonists to maintain endothelial function during or following treatments with chemotherapeutic agents, without affecting anti-tumor effectiveness.

scholarly journals A Contemporary Review of Immune Checkpoint Inhibitors in Advanced Clear Cell Renal Cell Carcinoma

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 919
Author(s):  
Eun-mi Yu ◽  
Laura Linville ◽  
Matthew Rosenthal ◽  
Jeanny B. Aragon-Ching
Keyword(s):  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Vascular Endothelial ◽  
Vegf Inhibitors ◽  
Cell Renal Cell Carcinoma ◽  
Improved Outcomes ◽  
Immune Oncology ◽  
Endothelial Growth Factor

The use of checkpoint inhibitors in advanced and metastatic renal cell carcinomas (RCCs) has rapidly evolved over the past several years. While immune-oncology (IO) drug therapy has been successful at resulting in improved responses and survival, combination therapies with immune checkpoint inhibitors and vascular endothelial growth factor (VEGF) inhibitors have further improved outcomes. This article reviews the landmark trials that have led to the approval of IO therapies, including the Checkmate 214 trial and combination IO/VEGF TKI therapies with Checkmate 9ER, CLEAR, and Keynote-426, and it includes a discussion on promising therapies moving in the future.

Chemotherapeutic Agents and the Kidney

2019 ◽  
pp. 253-264 ◽  
Author(s):  
Umut Selamet ◽  
Ramy M. Hanna ◽  
Anjay Rastogi ◽  
Ala Abudayyeh
Keyword(s):  
Targeted Therapy ◽  
Anticancer Agents ◽  
Checkpoint Inhibitors ◽  
Chemotherapeutic Agents ◽  
Vascular Endothelial ◽  
Cancer Treatments ◽  
Glomerular Diseases ◽  
Immune Mediated ◽  
Renal Tubular ◽  
Endothelial Growth Factor

Chemotherapeutic agents have toxicities that extend beyond their therapeutic effect on malignant cells, and the kidneys are involved in the metabolism of these agents. Kidney toxicity delay the elimination of anticancer drugs from the body and increase the risk of systemic toxicity. Conventional chemotherapeutics generally cause direct renal tubular injury and electrolyte wasting syndromes. Newer cancer treatments include targeted therapy and immunotherapy. Targeted therapy, especially the drugs that target vascular endothelial growth factor, disrupt the crosstalk between podocytes and endothelial cells of the glomerulus resulting in a spectrum of glomerular diseases. On the other hand, immune checkpoint inhibitors release the break on the immune system and can cause immune-mediated tubulointerstitial nephritis and glomerulonephritis similar to autoimmune diseases. This chapter summarizes nephrotoxicity profiles of some of the common conventional chemotherapeutics as well as newer anticancer agents.

scholarly journals Anti-PD-1, anti-VEGF, and temozolomide therapy in a patient with recurrent glioblastoma: a case report

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052095139
Author(s):  
Can Chen ◽  
Wenwei Zuo ◽  
Pan Yang ◽  
Yanling Zhang
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Checkpoint Inhibitors ◽  
Complete Response ◽  
Recurrent Glioblastoma ◽  
Vascular Endothelial ◽  
Case Presentation ◽  
Programmed Death ◽  
Endothelial Growth Factor

Background Patients suffering from postoperative recurrent glioblastoma have an extremely unfavorable outcome because there are no proven therapeutic options. The median overall survival for those with relapsed glioblastoma after surgery is only 7.5 months. Case presentation: Between March 2015 and October 2019, a 44-year-old female patient with recurrent glioblastoma was treated by our medical team. After several failed rounds of therapy, the patient was subsequently treated with the anti-programmed death (PD)-1 antibody nivolumab, anti-vascular endothelial growth factor (VEGF) antibody bevacizumab, and cytotoxic agent temozolomide. Results The patient showed a sustainable complete response to the regimen. To date, there have been no serious toxic side effects. As of October 2019 (the last follow-up), the patient has been in complete remission for 17 months since recurrence. Conclusion The experience of this complicated case indicates the possible application of immune checkpoint inhibitors, anti-angiogenesis agents, and cytotoxic reagents for recurrent glioblastoma. The administration of this three-agent regimen appears safe and effective. However, further clinical trials are warranted.

scholarly journals Emerging and Novel Treatments for Pituitary Tumors

2019 ◽  
Vol 8 (8) ◽  
pp. 1107 ◽  
Author(s):  
Ilie ◽  
Lasolle ◽  
Raverot
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Radionuclide Therapy ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Growth Factor Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Vascular Endothelial ◽  
Peptide Receptor ◽  
Radiological Response ◽  
Endothelial Growth Factor

A subset of pituitary neuroendocrine tumors (PitNETs) have an aggressive behavior, showing resistance to treatment and/or multiple recurrences in spite of the optimal use of standard therapies (surgery, conventional medical treatments, and radiotherapy). To date, for aggressive PitNETs, temozolomide (TMZ) has been the most used therapeutic option, and has resulted in an improvement in the five-year survival rate in responders. However, given the fact that roughly only one third of patients showed a partial or complete radiological response on the first course of TMZ, and even fewer patients responded to a second course of TMZ, other treatment options are urgently needed. Emerging therapies consist predominantly of peptide receptor radionuclide therapy (20 cases), vascular endothelial growth factor receptor-targeted therapy (12 cases), tyrosine kinase inhibitors (10 cases), mammalian target of rapamycin (mTOR) inhibitors (six cases), and more recently, immune checkpoint inhibitors (one case). Here, we present the available clinical cases published in the literature for each of these treatments. The therapies that currently show the most promise (based on the achievement of partial radiological response in a certain number of cases) are immune checkpoint inhibitors, peptide receptor radionuclide therapy, and vascular endothelial growth factor receptor-targeted therapy. In the future, further improvement of these therapies and the development of other novel therapies, their use in personalized medicine, and a better understanding of combination therapies, will hopefully result in better outcomes for patients bearing aggressive PitNETs.

scholarly journals Update on immunotherapy for renal cancer

Medwave ◽  
2021 ◽  
Vol 21 (05) ◽  
pp. e8202-e8202
Author(s):  
Rodrigo Canales Rojas
Keyword(s):  
Renal Cell Carcinoma ◽  
Vascular Endothelial Growth Factor ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Renal Cell Carcinoma ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

In the last decade, the development of immune checkpoint inhibitors have revolutionized the treatment of patients with advanced renal cell carcinoma, with the potential for dramatic changes in the therapeutic landscape. Nivolumab, a monoclonal antibody inhibitor of transmem-brane programmed cell death protein 1 (PD-1), was approved as monotherapy in 2015 for advanced renal cell carcinoma in patients previously treated with an agent targeting vascular endothelial growth factor. In April 2018, the combination of nivolumab and ipilimumab, a cytotoxic T-lymphocyte-associated antigen 4 inhibitor, was approved for patients with previously untreated intermediate- and poor-risk advanced renal cell carcinoma. Then, in 2019, combination therapies consisting of pembrolizumab (anti-PD-1) or avelumab (anti-PD-1 ligand, PD-L1) with axitinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) were also approved for use in all risk groups. This review pre-sents a brief historical review of the association between immunology and oncology; describes essential aspects of the mechanism of action of immune checkpoint inhibitors; discusses the current evidence regarding the clinical use of different immunotherapy regimens for the treatment of patients with renal cell carcinoma, both clear cell and other histological types; and provides general information on their adverse effects. The role of appropriate patient selection is analyzed to allow individualization of therapy and improve the already promising results. Finally, per-spectives on the future use of immune checkpoint inhibitors to treat renal cancer are discussed.

Abstract 12563: Retrospective Analysis of Cardiovascular Events With the Use of Immune Checkpoint Inhibitors

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tushar Tarun ◽  
Brian P Bostick ◽  
Deepa Baswaraj ◽  
Nishchayjit Basra ◽  
Meeshal Khan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Retrospective Analysis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Multiple Organ ◽  
Fulminant Myocarditis ◽  
Organ Systems ◽  
History Of

Introduction: Immune checkpoint inhibitors have emerged as a promising, novel therapy for multiple malignancies. Immune-related adverse reactions pose a serious concern with use of these agents and reportedly involve multiple organ systems, notably cardiotoxicity. Early identification and management of these adverse events is essential in the prevention of morbidity and mortality. Hypothesis: Immune checkpoint inhibitors cause multiple cardiotoxic effects, and patients with prior cardiac history have a higher likelihood of cardiotoxicity. Methods: 1. A retrospective analysis of 150 patients was performed who had received immunotherapy with either the cytotoxic T lymphocyte associated antigen 4 inhibitors (CTLA4) or with the programmed cell death inhibitors (PD1) or programmed death-ligand 1 (PD-L1) inhibitors for a period of two years at a Tertiary health Care from 7/1/2016-6/30/2018. 2. Patients' cardiac diagnoses prior to the initiation of therapy were noted and included, including history of heart failure, coronary artery disease, atrial fibrillation, and sudden cardiac arrest. 3. Patients’ clinic visits and hospitalizations with admitting and discharge diagnosis, electrocardiogram, echocardiogram, troponin T, and NT-proBNP were reviewed. Results: 6% of patients had new onset heart failure (both preserved and reduced), 1.3% had evidence of myocardial infarction, 2% had new atrial fibrillation with rapid ventricular rate, and 0.6% had fulminant myocarditis. Of patients with new cardiac events, 60% had a history of cardiac disease, which was significantly higher than in patients without (p< 0.05). There were no age or sex differences between the groups with and without cardiotoxicity. Conclusion: Immunotherapy with immune checkpoint inhibitors have broadened the horizon for treatment of multiple solid and hematological malignancies. Nonetheless, new adverse effects on multiple organ systems, specifically cardiac involvement, occur with these therapies, which are important and potentially detrimental toxicities. Patients with a history of prior cardiovascular disease have higher likelihood to develop cardiotoxicity.

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