cardiovascular-agents and Neoplasms

Cancer metabolic plasticity, including changes in fatty acid metabolism utilisation, is now widely appreciated as a key driver for cancer cell growth, survival and malignancy. Hence, cancer metabolic pathways have been the focus of much recent drug development. Perhexiline is a prophylactic antianginal drug known to act by inhibiting carnitine palmitoyltransferase 1 (CPT1) and 2 (CPT2), mitochondrial enzymes critical for fatty acid metabolism. In this review, we discuss the growing evidence that perhexiline has potent anti-cancer properties when tested as a monotherapy or in combination with traditional chemotherapeutics. We review the CPT1/2 dependent and independent mechanisms of its anti-cancer activities. Finally, we speculate on the clinical feasibility and utility of repurposing perhexiline as an anti-cancer agent, its limitations including known side effects and its potential added benefit of limiting cardiotoxicity induced by other chemotherapeutics.

Topics: Cardiovascular Agents; Fatty Acids; Humans; Mitochondria; Neoplasms; Perhexiline

Cyclin-dependent kinases (CDKs) are involved in many crucial processes, such as cell cycle and transcription, as well as communication, metabolism, and apoptosis. The kinases are organized in a pathway to ensure that, during cell division, each cell accurately replicates its DNA, and ensure its segregation equally between the two daughter cells. Deregulation of any of the stages of the cell cycle or transcription leads to apoptosis but, if uncorrected, can result in a series of diseases, such as cancer, neurodegenerative diseases (Alzheimer's or Parkinson's disease), and stroke. This review presents the current state of knowledge about the characteristics of cyclin-dependent kinases as potential pharmacological targets.

Topics: Alzheimer Disease; Animals; Antineoplastic Agents; Apoptosis; Cardiomegaly; Cardiovascular Agents; Cell Cycle; Cyclin-Dependent Kinases; Cyclins; Gene Expression Regulation; Humans; Neoplasms; Neuroprotective Agents; Parkinson Disease; Protein Kinase Inhibitors; Saccharomyces cerevisiae; Stroke

Cardiovascular diseases (CVD) and cancer are still the leading causes of death. There are many common etiologic factors, especially smoking and obesity. Therefore, it is not uncommon for CVD and cancer to coexist. Drug-drug interactions (DDIs) inevitably occur in this group of patients, where polypharmacy is increasing due to older age and multiple comorbidities. However, multidisciplinary studies, especially close collaboration of medical oncologists and cardiologists, who deals with the diagnosis and treatment of these diseases, awareness and preventive approaches to DDIs may reduce serious morbidity and mortality. In this review, information about the common treatments used in cardiology and oncology and possible DDIs are discussed.

Topics: Aged; Antineoplastic Agents; Cardiology; Cardiovascular Agents; Cardiovascular Diseases; Drug Interactions; Humans; Neoplasms

Therapeutic ultrasound strategies that harness the mechanical activity of cavitation nuclei for beneficial tissue bio-effects are actively under development. The mechanical oscillations of circulating microbubbles, the most widely investigated cavitation nuclei, which may also encapsulate or shield a therapeutic agent in the bloodstream, trigger and promote localized uptake. Oscillating microbubbles can create stresses either on nearby tissue or in surrounding fluid to enhance drug penetration and efficacy in the brain, spinal cord, vasculature, immune system, biofilm or tumors. This review summarizes recent investigations that have elucidated interactions of ultrasound and cavitation nuclei with cells, the treatment of tumors, immunotherapy, the blood-brain and blood-spinal cord barriers, sonothrombolysis, cardiovascular drug delivery and sonobactericide. In particular, an overview of salient ultrasound features, drug delivery vehicles, therapeutic transport routes and pre-clinical and clinical studies is provided. Successful implementation of ultrasound and cavitation nuclei-mediated drug delivery has the potential to change the way drugs are administered systemically, resulting in more effective therapeutics and less-invasive treatments.

Topics: Bacterial Infections; Blood-Brain Barrier; Cardiovascular Agents; Drug Delivery Systems; Humans; Immunotherapy; Microbubbles; Neoplasms; Thrombolytic Therapy; Ultrasonic Therapy

Patients with cancer survivors are at increased risk of cardiovascular disease(CVD). Cardio-oncology has developed as a new discipline with the advances in cancer treatment. There are many new challenges for the clinician and a new frontier for research and investigation. There is an urgent need for further study on the prevention of cardiovascular toxicity. Imperatorin (IMP) is a natural form of coumarin and extract from several plants with diver's pharmacokinetic effects, including antioxidant and anti-inflammatory properties. This review focus on the molecular mechanisms and pharmacological effects of Imperatorin maybe provide potential cancer and cardiovascular protection that targets IMP. Further studies are required to elucidate the entire spectrum of cytotoxic activities of these compounds to validate and expand their preclinical and clinical applications and to clarify the potential role of IMP.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Furocoumarins; Humans; Inflammation Mediators; Neoplasms; Oxidative Stress; Signal Transduction

Cardiovascular (CV) disease and cancer are the leading causes of death.1,2 Over the last decades, it has been appreciated that both CV disease and cancer are more common in individuals in whom risk factors for disease development accumulate, and preventative measures have been extremely important in driving down the incidence of disease.3-6 In general, the field of epidemiology, risk reduction, and preventative trials is divided into health care professionals who have an interest in either CV disease or cancer. As a result, the medical literature and medical practice has largely focused on the one disease, or the other. However, human individuals do not behave according to this dogma. Emerging data clearly suggest that identical risk factors may lead to CV disease in the one individual, but may cause cancer in another, or even both diseases in the same individual. This overlap exists between risk factors that are historically classified as 'CV risk factors' as these factors do equally strong predict cancer development. Therefore, we propose that a holistic approach might better estimate actual risks for CV disease and cancer. In this review, we summarize current insights in common behavioural risk factors for heart failure, being the most progressed and lethal form of CV disease, and cancer.

Topics: Antineoplastic Agents; Cardiotoxicity; Cardiovascular Agents; Heart Failure; Humans; Neoplasms; Prognosis; Risk Assessment; Risk Factors

Inflammation participates in the pathogenesis of both cancer and cardiovascular disease. This review examines the mechanistic commonalities between these two scourges of humanity through the lens of inflammation biology. Inflammatory pathways contribute to the initiation, the progression, and the complication of both malignant tumours and atherosclerotic plaques. Modulation of inflammatory pathways have proven transformative in the treatment of cancers and have crossed the threshold of clinical reality as treatments to reduce the risk of cardiovascular events. The finding that clonal haematopoiesis drives both leukaemia and cardiovascular events provides yet another link between these two seemingly disparate diseases. The nascent specialty of cardio-oncology has initially focused on the cardiovascular complications of cancer therapies. The recognition of a more profound pathophysiologic connection between cancer and cardiovascular diseases should expand the concept of cardio-oncology. Embracing the mechanistic connection and transcending traditional barriers between disciplines offers immense opportunities for speeding innovative research that can address the growing burden of both cancer and cardiovascular disease.

Topics: Age Factors; Aging; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Cardiology; Cardiovascular Agents; Cardiovascular Diseases; Cytokines; Humans; Inflammation; Inflammation Mediators; Medical Oncology; Neoplasms; Prognosis; Risk Assessment; Risk Factors; Signal Transduction; Translational Research, Biomedical

Research on the concept of biological overlap between cardiovascular and oncological diseases is gaining momentum. In fact, in both conditions, the malfunction of common regulatory mechanisms, such as the renin-angiotensin system (RAS), sympathetic nervous system (SNS), coagulation cascade, sodium-potassium ATP-ases, and mevalonate pathway, occurs. Thus, targeting these mechanisms with well-known cardiology drugs, including angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), β-adrenergic receptor blockers, statins, cardiac glycosides (CGs), and low-molecular-weight heparins (LMWHs), could be a novel, promising adjuvant strategy in cancer management. Thus, here we discuss the idea of repurposing cardiology drugs in oncology based on available preclinical and clinical data.

Topics: Animals; Anticoagulants; Cardiac Glycosides; Cardiovascular Agents; Drug Repositioning; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mevalonic Acid; Neoplasms; Renin-Angiotensin System; Sympathetic Nervous System

The preventive effects of olive oil against different diseases have been attributed to its high phenolic compound content. The objective of this study was to examine available scientific evidence on the beneficial effects against chronic diseases of olive oil phenolic compounds.. This article examines recently published data on olive oil phenolic compounds and their potential benefits in the prevention of cardiovascular disease, cancer, neurodegenerative disease, and osteoporosis.. The antioxidant, anti-proliferative, pro-apoptotic, and anti-inflammatory activities of olive oil phenolic compounds have preventive effects against heart disease and cancer. These compounds also exert neuroprotective and neuromodulator effects against neurodegenerative disease, inhibiting the development of amyloid plaques. Finally, they are known to protect against osteoporosis, favoring bone regeneration.. Dietary intake of olive oil can be recommended by healthcare professionals as an important source of phenolic compounds that play a role in the prevention of chronic disease and the consequent improvement in quality of life.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Bone Density Conservation Agents; Cardiovascular Agents; Cardiovascular Diseases; Diet, Healthy; Humans; Neoplasms; Neurodegenerative Diseases; Neuroprotective Agents; Olive Oil; Osteoporosis; Phenols; Protective Factors; Risk Factors

Multi-target and combinatorial therapies have been focused for the past several decades. These approaches achieved considerable therapeutic efficacy by modulating the activities of the targets in complex diseases such as HIV-1 infection, cancer and diabetes disease. Most of the diseases cannot be treated efficiently in terms of single gene target, because it involves the cessation of the coordinated function of distinct gene groups. Most of the cellular components work efficiently by interacting with other cellular components and all these interactions together represent interactome. This interconnectivity shows that a defect in a single gene may not be restricted to the gene product itself, but may spread along the network. So, drug development must be based on the network-based perspective of disease mechanisms. Many systematic diseases like neurodegenerative disorders, cancer and cardiovascular cannot be treated efficiently by the single gene target strategy because these diseases involve the complex biological machinery. In clinical trials, many mono-therapies have been found to be less effective. In mono-therapies, the long term treatment, for the systematic diseases make the diseases able to acquired resistance because of the disease nature of the natural evolution of feedback loop and pathway redundancy. Multi-target drugs might be more efficient. Multi-target therapeutics might be less vulnerable because of the inability of the biological system to resist multiple actions. In this study, we will overview the recent advances in the development of methodologies for the identification of drug target interaction and its application in the poly-pharmacology profile of the drug.

Topics: Antineoplastic Agents; Cardiovascular Agents; Cardiovascular Diseases; Drug Evaluation, Preclinical; Gene Regulatory Networks; Humans; Molecular Targeted Therapy; Neoplasms; Neurodegenerative Diseases; Neuroprotective Agents; Polypharmacology

This review summarizes recent progress in understanding the role of p53-upregulated mediator of apoptosis (PUMA) in molecular pathways with respect to its potential therapeutic applications. Particular emphasis is given to the PUMA´s role in ionizing radiation-induced signalling as radiotoxicity of normal tissue is mediated mostly via apoptosis. PUMA and its p53-dependent and p53- independent induction are described and potential use as a new target for the development of radioprotective agents is suggested. Further implications, including targeting PUMA to prevent and treat cardiovascular and neurodegenerative diseases, are also discussed together with an overview of other therapeutic applications. Finally, basic chemical structures for the development of novel PUMA modulators such as pifithrine derivatives, kinase inhibitors or modulators of Bcl-2 protein family are described.

Topics: Apoptosis; Apoptosis Regulatory Proteins; Cardiovascular Agents; Cardiovascular Diseases; DNA Damage; Humans; Molecular Targeted Therapy; Neoplasms; Neurodegenerative Diseases; Neuroprotective Agents; Protein Binding; Proto-Oncogene Proteins; Radiation Injuries; Radiation Tolerance; Radiation-Protective Agents; Signal Transduction; Tumor Suppressor Protein p53

The number of cancer survivors is exponentially increasing worldwide, due to both advances in cancer detection and treatment strategies, as well as the aging and growth of the population. This decrease in cancer mortality has brought forth a concurrent increase of non-ischemic (toxic) dilated cardiomyopathy in the survivor population, also known as cancer therapeutics-induced cardiomyopathy (CTIC). The optimal pharmacological management for this condition is still elusive, and hence, the focus of this work.. Our review of the literature did not identify any prospective randomized clinical trial of CTIC in adult cancer survivors, neither published nor in progress. However, available data seem to suggest that, when managed with standard guideline-derived medical therapy, the outcomes of CTIC are comparable to that of idiopathic dilated cardiomyopathy (IDC). Nonetheless, the evidence behind this strategy is inadequate. Until new information becomes available, pharmacological management of CTIC must parallel that of IDC. However, implementation of such may be hindered by other cancer therapeutics-induced comorbidities and conditioned by the particular effects of heart failure pharmacotherapy on cancer outcomes. This work succinctly reviews these three areas, in the context of adult cancer survivors.

Topics: Adult; Cancer Survivors; Cardiomyopathies; Cardiovascular Agents; Comorbidity; Global Health; Heart Failure; Humans; Neoplasms

Recent epidemiological analyses suggest that incident cancer may be more common among patients with preexisting heart failure (HF) than in patients without HF. Arguments against this notion have been the increased chance of co-occurrence of 2 high-prevalence conditions and increased tumor detection in patients with HF because of intensified medical observation. However, biological data lend support to the hypothesis that HF is an oncogenic condition. Neurohormonal activation has been related to cancer initiation, progression, and dissemination by studies not specifically focusing on HF, which are now reappraised in the light of the emerging evidence that tumors are diagnosed more often in HF than control cohorts. Furthermore, a thought-provoking scenario to be considered is that a systemically perturbed milieu, where low-grade inflammation plays a primary role, leads to both HF and malignancy, thus connecting 1 disease to another. Postischemic HF has been shown to promote tumor growth in an animal model. Exploring these and other pathways potentially linking HF to malignancy is a new and exciting field of research, with the ultimate goal of answering the question of whether HF does promote cancer.

Topics: Antineoplastic Agents; Cardiovascular Agents; Comorbidity; Heart Failure; Humans; Incidence; Inflammation Mediators; Neoplasms; Neurotransmitter Agents; Oxidative Stress; Prognosis; Renin-Angiotensin System; Risk Assessment; Risk Factors; Signal Transduction

Cardiovascular disease (CVD) and cancer are leading causes of mortality and morbidity worldwide. Strategies to improve their treatment and prevention are global priorities and major focus of World Health Organization's joint prevention programs. Emerging evidence suggests that modifiable risk factors including diet, sedentary lifestyle, obesity and tobacco use are central to the pathogenesis of both diseases and are reflected in common genetic, cellular, and signaling mechanisms. Understanding this important biological overlap is critical and may help identify novel therapeutic and preventative strategies for both disorders. In this review, we will discuss the shared genetic and molecular factors central to CVD and cancer and how the strategies commonly used for the prevention of atherosclerotic vascular disease can be applied to cancer prevention.

Topics: Animals; Anticarcinogenic Agents; Biomarkers, Tumor; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Cell Transformation, Neoplastic; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Risk Factors; Signal Transduction

Phospholipase D2 (PLD2) is a lipid-signaling enzyme that produces the signaling molecule phosphatidic acid (PA) by catalyzing the hydrolysis of phosphatidylcholine (PC). The molecular characteristics of PLD2, the mechanisms of regulation of its activity, its functions in the signaling pathway involving PA and binding partners, and its role in cellular physiology have been extensively studied over the past decades. Although several potential roles of PLD2 have been proposed based on the results of molecular and cell-based studies, the pathophysiological functions of PLD2 in vivo have not yet been fully investigated at the organismal level. Here, we address accumulated evidences that provide insight into the role of PLD2 in human disease. We summarize recent studies using animal models that provide direct evidence of the function of PLD2 in several pathological conditions such as vascular disease, immunological disease, and neurological disease. In light of the use of recently developed PLD2-specific inhibitors showing potential in alleviating pathological conditions, improving our understanding of the role of PLD2 in human disease would be necessary to target the regulation of PLD2 activity as a therapeutic strategy.

Topics: Animals; Antineoplastic Agents; Cardiovascular Agents; Gene Expression Regulation; Humans; Immune System Diseases; Immunologic Factors; Mice; Neoplasms; Nervous System Diseases; Neuroprotective Agents; Phosphatidic Acids; Phosphatidylcholines; Phospholipase A2 Inhibitors; Phospholipase D; Signal Transduction; Vascular Diseases

The macrocycles representing a unique chemical structure bridging conventional small molecules and large biomolecules, have attracted more and more attention in drug discovery over the past decade, and tremendous progress has been made toward the macrocyclization synthesis and structure diversification recently. Because of their favored size, flexibility and complexity, macrocycles can engage previously undruggable targets through numerous and spatially distributed binding interactions, and offer many privileged features including high potency, prominent selectivity, as well as favorable pharmacokinetics properties, and unique intellectual property(IP) space, and even safety profiles, etc. Currently around 70 macrocyclic molecules have been approved for clinical therapy, over 76 macrocycles are being evaluated in clinical trials from phase I to phase III. It is believed that the macrocycles will play more and more important role in the future, and provide very distinctive and promising opportunities for drug discovery along with the development of synthetic methodology, phenotypical screening, and computational studies.

Topics: Anti-Infective Agents; Antineoplastic Agents, Phytogenic; Cardiovascular Agents; Cardiovascular Diseases; Drug Discovery; Humans; Immune System Diseases; Macrocyclic Compounds; Neoplasms

Aging, cancer, and chronic disease have remained at the forefront of basic biological research for decades. Within this context, significant attention has been paid to the role of telomerase, the enzyme responsible for lengthening telomeres, the nucleotide sequences located at the end of chromosomes found in the nucleus. Alterations in telomere length and telomerase activity are a common denominator to the underlying pathology of these diseases. While nuclear-specific, telomere-lengthening effects of telomerase impact cellular/organismal aging and cancer development, non-canonical, extra-nuclear, and non-telomere-lengthening contributions of telomerase have only recently been described and their exact physiological implications are ill defined. Although the mechanism remains unclear, recent reports reveal that the catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), regulates levels of mitochondrial-derived reactive oxygen species (mtROS), independent of its established role in the nucleus. Telomerase inhibition has been the target of chemotherapy (directed or indirectly) for over a decade now, yet no telomerase inhibitor is FDA approved and few are currently in late-stage clinical trials, possibly due to underappreciation of the distinct extra-nuclear functions of telomerase. Moreover, evaluation of telomerase-specific therapies is largely limited to the context of chemotherapy, despite reports of the beneficial effects of telomerase activation in the cardiovascular system in relation to such processes as endothelial dysfunction and myocardial infarction. Thus, there is a need for better understanding of telomerase-focused cell and organism physiology, as well as development of telomerase-specific therapies in relation to cancer and extension of these therapies to cardiovascular pathologies. This review will detail findings related to telomerase and evaluate its potential to serve as a therapeutic target.

Topics: Animals; Antineoplastic Agents; Cardiovascular Agents; Cardiovascular Diseases; Enzyme Activation; Enzyme Activators; Enzyme Inhibitors; Humans; Molecular Targeted Therapy; Neoplasms; Signal Transduction; Telomerase; Telomere Homeostasis; Telomere Shortening

Research and development of new drugs requires both long time and high costs, whereas safety and tolerability profiles make the success rate of approval very low. Drug repurposing, applying known drugs and compounds to new indications, has been noted recently as a cost-effective and time-unconsuming way in developing new drugs, because they have already been proven safe in humans. In this review, we discuss drug repurposing of approved cardiovascular drugs, such as aspirin, beta-blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, cardiac glycosides and statins. Regarding anti-tumor activities of these agents, a number of experimental studies have demonstrated promising pleiotropic properties, whereas all clinical trials have not shown expected results. In pathological conditions other than cancer, repurposing of cardiovascular drugs is also expanding. Numerous experimental studies have reported possibilities of drug repurposing in this field and some of them have been tried for new indications ('bench to bedside'), while unexpected results of clinical studies have given hints for drug repurposing and some unknown mechanisms of action have been demonstrated by experimental studies ('bedside to bench'). The future perspective of experimental and clinical studies using cardiovascular drugs are also discussed.

Topics: Cardiovascular Agents; Drug Approval; Drug Repositioning; Humans; Neoplasms

Cardiac glycosides, the cardiotonic steroids such as digitalis have been in use as heart ailment remedy since ages. They manipulate the renin-angiotensin axis to improve cardiac output. However; their safety and efficacy have come under scrutiny in recent times, as poisoning and accidental mortalities have been observed. In order to better understand and exploit them as cardiac ionotropes, studies are being pursued using different cardiac glycosides such as digitoxin, digoxin, ouabain, oleandrin etc. Several cardiac glycosides as peruvoside have shown promise in cancer control, especially ovary cancer and leukemia. Functional variability of these glycosides has revealed that not all cardiac glycosides are alike. Apart from their specific affinity to sodium-potassium ATPase, their therapeutic dosage and behavior in poly-morbidity conditions needs to be considered. This review presents a concise account of the key findings in recent years with adequate elaboration of the mechanisms. This compilation is expected to contribute towards management of cardiac, cancer, even viral ailments.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cardenolides; Cardiac Glycosides; Cardiovascular Agents; Enzyme Inhibitors; Heart Diseases; Humans; Neoplasms; Renin-Angiotensin System; Saponins; Sodium-Potassium-Exchanging ATPase

Acetylsalicylic acid (aspirin) is a prototypic cyclooxygenase (COX) inhibitor. It was synthesized serendipitously from a natural compound, i.e., salicylic acid, with known analgesic activity. This chemical modification, obtained for the first time in an industrial environment in 1897, endowed aspirin with the unique capacity of acetylating and inactivating permanently COX-isozymes. Traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) were developed to mimic the pharmacological effects of aspirin, using aspirin-sensitive experimental models of pain and inflammation as the template for screening new chemical entities. Among the tNSAIDs, some were endowed with moderate COX- selectivity (e.g., diclofenac), but no studies of sufficient size and duration were performed to show any clinically relevant difference between different members of the class. Similarly, no serious attempts were made to unravel the mechanisms involved in the shared therapeutic and toxic effects of tNSAIDs until the discovery of COX-2. This led to characterizing their main therapeutic effects as being COX-2-dependent and their gastrointestinal (GI) toxicity as being COX-1-dependent, and provided a rationale for developing a new class of selective COX-2 inhibitors, the coxibs. This review will discuss the clinical pharmacology of tNSAIDs and coxibs, and the clinical read-outs of COX-isozyme inhibition. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance."

Topics: Animals; Anticarcinogenic Agents; Cardiovascular Agents; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Gastrointestinal Diseases; Heart Diseases; Humans; Inflammation; Isoenzymes; Molecular Structure; Neoplasms; Risk Factors; Signal Transduction; Structure-Activity Relationship

The erythropoietin-producing hepatocellular carcinoma (Eph) receptor tyrosine kinase family plays important roles in developmental processes, adult tissue homeostasis, and various diseases. Interaction with Eph receptor-interacting protein (ephrin) ligands on the surface of neighboring cells triggers Eph receptor kinase-dependent signaling. The ephrins can also transmit signals, leading to bidirectional cell contact-dependent communication. Moreover, Eph receptors and ephrins can function independently of each other through interplay with other signaling systems. Given their involvement in many pathological conditions ranging from neurological disorders to cancer and viral infections, Eph receptors and ephrins are increasingly recognized as attractive therapeutic targets, and various strategies are being explored to modulate their expression and function. Eph receptor/ephrin upregulation in cancer cells, the angiogenic vasculature, and injured or diseased tissues also offer opportunities for Eph/ephrin-based targeted drug delivery and imaging. Thus, despite the challenges presented by the complex biology of the Eph receptor/ephrin system, exciting possibilities exist for therapies exploiting these molecules.

Topics: Animals; Antineoplastic Agents; Antiviral Agents; Cardiovascular Agents; Cardiovascular Diseases; Drug Design; Ephrins; Humans; Ligands; Molecular Targeted Therapy; Neoplasms; Nervous System Diseases; Receptors, Eph Family; Signal Transduction; Virus Diseases

The role of chemokines and their receptors in controlling several physiological and pathological processes has only become evident in the last couple of years. From a sole function of chemo-attraction, our view on chemokine receptor activation has switched to the regulation of pleiotropic signaling pathways influencing numerous molecular and cellular processes. The large number of chemokines and receptors and hence possible combinations of chemokine-chemokine receptor interactions, as well as the expression profiles of chemokines and chemokine receptors within particular cell types, has contributed to the complexity of chemokine receptor signaling as we see it today. The chemokine CCL2 and its main chemokine receptor CCR2 have been implicated in the pathogenesis of several different disease processes, including vascular permeability and attraction of immune cells during metastasis, a number of different neurological disorders, autoimmune disease, obesity, and atherosclerosis. Here we review recent findings on the role of the CCL2-CCR2 axis in the regulation of these diseases. We believe that research has only gained a first glimpse of what chemokines can control and what the underlying mechanisms are. There is certainly more to be found that will - with high certainty - have strong implications for clinical applications in the near future.

Topics: Animals; Antineoplastic Agents; Autocrine Communication; Autoimmune Diseases; Cardiovascular Agents; Cardiovascular Diseases; Central Nervous System; Chemokine CCL2; Drug Design; Humans; Immunosuppressive Agents; Metabolic Syndrome; Molecular Targeted Therapy; Neoplasms; Nervous System Diseases; Receptors, CCR2; Signal Transduction; Tumor Microenvironment

The second messenger cyclic adenosine monophosphate (cAMP) can bind and activate protein kinase A (PKA). The cAMP/PKA system is ubiquitous and involved in a wide array of biological processes and therefore requires tight spatial and temporal regulation. Important components of the safeguard system are the A-kinase anchoring proteins (AKAPs), a heterogeneous family of scaffolding proteins defined by its ability to directly bind PKA. AKAPs tether PKA to specific subcellular compartments, and they bind further interaction partners to create local signalling hubs. The recent discovery of new AKAPs and advances in the field that shed light on the relevance of these hubs for human disease highlight unique opportunities for pharmacological modulation. This review exemplifies how interference with signalling, particularly cAMP signalling, at such hubs can reshape signalling responses and discusses how this could lead to novel pharmacological concepts for the treatment of disease with an unmet medical need such as cardiovascular disease and cancer.

Topics: A Kinase Anchor Proteins; Amino Acid Sequence; Animals; Antineoplastic Agents; Cardiovascular Agents; Cardiovascular Diseases; Conserved Sequence; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Humans; Molecular Sequence Data; Molecular Targeted Therapy; Neoplasms; Protein Interaction Maps; Second Messenger Systems

Cancer most commonly arises in the elderly who are often burdened with comorbidities. Medications used for treating these comorbidities may alter cancer prognosis. Understanding the impact of these medications on cancer is important in order to make effective evidence-based decisions about managing comorbidities while improving cancer outcomes.. The evidence on diabetes, statins, antihypertensive and anti-inflammatory medications and their association with cancer recurrence and cancer-specific mortality are reviewed. The strengths and limitations of the existing literature, the current state of the field and future directions are discussed.. Metformin and aspirin were associated with a reduced risk of cancer recurrence and cancer-specific mortality. The evidence for statins and antihypertensive medications on cancer survival was inconsistent. There were few studies to suggest that any of the medication classes of interest were associated with negative effects on cancer survival. Methodological shortcomings within observational studies, such as confounding, distinguishing between use of medications pre-cancer versus post-cancer diagnosis/treatment, misclassification of exposures/outcomes, informative censoring and competing risks, must be considered. New observational studies addressing these limitations are essential. Some clinical trials are underway to further investigate the beneficial effects of these drugs and completed trials have confirmed results demonstrated in observational studies.

Topics: Aged; Anti-Inflammatory Agents; Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Neoplasm Recurrence, Local; Neoplasms; Prognosis; Survival

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Drug Delivery Systems; ErbB Receptors; Humans; Neoplasms; Receptor, ErbB-2

Topics: Animals; Cardiovascular Agents; Cardiovascular System; Drug Delivery Systems; Drug Interactions; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Neoplasms

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cardiovascular Agents; Cardiovascular System; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Humans; Neoplasms

Cereals and legumes are key components of a healthy and balanced diet. Accordingly, many national nutritional guidelines emphasize their health promoting properties by placing them at the base of nutritional food pyramids. This concept is further validated by the observed correlation between a lower risk and occurrence of chronic diseases and the adherence to dietary patterns, like the Mediterranean diet, in which cereal grains, legumes and derived products represent a staple food. In the search for a dietary approach to control/prevent chronic degenerative diseases, protein derived bioactive peptides may represent one such source of health-enhancing components. These peptides may already be present in foods as natural components or may derive from hydrolysis by chemical or enzymatic treatments (digestion, hydrolysis or fermentation). Many reports are present in the literature regarding the bioactivity of peptides in vitro and a wide range of activities has been described, including antimicrobial properties, blood pressure-lowering (ACE inhibitory) effects, cholesterol-lowering ability, antithrombotic and antioxidant activities, enhancement of mineral absorption/bioavailability, cyto- or immunomodulatory effects, and opioid-like activities. However it is difficult to translate these observed effects to human. In fact, the active peptide may be degraded during digestion, or may not be absorbed or reach the target tissues at a concentration necessary to exert its function. This review will focus on bioactive peptides identified in cereals and legumes, from an agronomical and biochemical point of view, including considerations about requirements for the design of appropriate clinical trials necessary for the assessment of their nutraceutical effect in vivo.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Cardiovascular Agents; Clinical Trials as Topic; Edible Grain; Fabaceae; Humans; Neoplasms; Peptides

Future innovative therapies targeting cardiovascular disease (CVD) have the potential to improve health outcomes and to contain rising healthcare costs. Unsustainable increases in the size, cost and duration of clinical trial programs necessary for regulatory approval, however, threaten the entire innovation enterprise. Rising costs for clinical trials are due in large part to increasing demands for hard cardiovascular clinical endpoints as measures of therapeutic efficacy. The development and validation of predictive and surrogate biomarkers, as laboratory or other objective measures predictive or reflective of clinical endpoints, are an important part of the solution to this challenge. This review will discuss insights applicable to CVD derived from the use of predictive biomarkers in oncologic drug development, the evolving role of high density lipoprotein (HDL) in CVD drug development and the impact biomarkers and surrogates have on the continued investment from multiple societal sources critical for innovative CVD drug discovery and development.

Topics: Biomarkers; Cardiovascular Agents; Cardiovascular Diseases; Cholesterol, HDL; Clinical Trials as Topic; Drug Approval; Drug Discovery; Humans; Neoplasms

Piper has been used for long timelike condiment and food, but also in traditional medicine around of the world. This work resumes the available and up to date work done on members of the Piperaceae family and their uses for therapeutic purposes.. Information on Piper genus was gathered via internet using scientific databases such as Scirus, Google Scholar, CAB-abstracts, MedlinePlus, Pubmed, SciFinder, Scopus and Web of Science.. The largeleafed perennial plant Piper is used for its spicy aromatic scent and flavor. It has an important presence in the cuisine of different cultures. Another quality of these plants is their known medicinal properties. It has been used as emollient, antirheumatic, diuretic, stimulant, abortifacient, anti-inflammatory, antibacterial, antifungal and antidermatophytic. A survey of the literature shows that the genus Piper is mainly known for its alkaloids with cytotoxic, chemopreventive, antimetastatic and antitumor properties in several types of cancer. Studies of its alkaloids highlight the existence of various potential leads to develop new anti-cancer agents. Modern pharmacology studies have demonstrated that its crude extracts and active compounds possess wide pharmacological activities, especially asantioxidant, anti-depressive, hepatoprotective, antimicrobial, anti-obesity, neuropharmacological, to treat cognitive disorders, anti-hyperlipidemic, anti-feedant, cardioactive, immuno-enhancing, and anti-inflamatory. All this evidence supporting its traditional uses.. This review summarizes the up-to-date and comprehensive information concerning the botany, traditional use, phytochemistry and pharmacology of Piper together with its toxicology, and discusses the possible trend and scope for further research on Piper in the future.

Topics: Alkaloids; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-Obesity Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Cardiovascular Agents; Cardiovascular Diseases; Central Nervous System Agents; Cognition Disorders; Humans; Neoplasms; Obesity; Piper; Plant Extracts; Platelet Aggregation Inhibitors

Focal adhesions (FA) are important mediators of endothelial cytoskeletal interactions with the extracellular matrix (ECM) via transmembrane receptors, integrins and integrin-associated intracellular proteins. This communication is essential for a variety of cell processes including EC barrier regulation and is mediated by the non-receptor protein tyrosine kinase, focal adhesion kinase (FAK). As FA mediate the basic response of EC to a variety of stimuli and FAK is essential to these responses, the idea of targeting EC FAK as a therapeutic strategy for an assortment of diseases is highly promising. In particular, inhibition of FAK could prove beneficial in a variety of cancers via effects on EC proliferation and angiogenesis, in acute lung injury (ALI) via the attenuation of lung vascular permeability, and in rheumatoid arthritis via reductions in synovial angiogenesis. In addition, there are potential therapeutic benefits of FAK inhibition in cardiovascular disease and diabetic nephropathy as well. Several drugs that target EC FAK are now in existence and include agents currently under investigation in preclinical models as well as drugs that are readily available such as the sphingolipid analog FTY720 and statins. As the role of EC FAK in the pathogenesis of a variety of diseases continues to be explored and new insights are revealed, drug targeting of FAK will continue to be an important area of investigation and may ultimately lead to highly novel and effective strategies to treat these diseases.

Topics: Acute Lung Injury; Angiogenesis Inhibitors; Animals; Antirheumatic Agents; Arthritis, Rheumatoid; Cardiovascular Agents; Cardiovascular Diseases; Diabetic Nephropathies; Endothelial Cells; Focal Adhesion Protein-Tyrosine Kinases; Humans; Neoplasms; Neovascularization, Pathologic; Protein Kinase Inhibitors; Respiratory System Agents; Signal Transduction

To prevent potential drug-drug interaction, lists of cautioned or prohibited (C/P) drugs are commonly included in protocols of phases I and II cancer trials. Heterogeneity among lists may affect patient eligibility and comparability of results.. Protocols of phase I/II trials conducted at an academic cancer centre between 2004 and 2009 were reviewed. All C/P drugs were collected and compared among trials.. Of 100 protocols reviewed, 77 protocols include lists of C/P drugs to prevent CYP3A4-, 2C9- and 2C19-related interactions and/or QT interval prolongation. Sixty-five protocols evaluating 38 unique study drugs include lists of CYP3A4-related C/P drugs. These lists contain 0-137 inhibitors [coefficient of variation (CV): 123%], 0-20 inducers (CV: 57%) and 10-157 substrates (CV: 76%). There is a high degree of inconsistency among protocols of the same study drug or from the same originator. Heterogeneity is also common for lists of C/P CYP2C9 and 2C19 drugs and for QT interval prolongation drugs. Approximately 20% protocols contain potential sources of confusion in their drug lists.. There is high degree of heterogeneity among lists of drugs C/P in protocols of oncology phase I/II trials. There is an urgent need to standardize these lists.

Topics: Antineoplastic Agents; Cardiovascular Agents; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Neoplasms; Practice Guidelines as Topic

Despite continuous improvements in management of patients with cancer, cardiac side-effects still account for a substantial limitation of chemotherapy. Evaluation of cardiac toxicity in patients includes consideration of biomarkers such as cardiac troponins and B-type natriuretic peptides, together with non-invasive imaging in the form of 2D-, 3D-, or strain-echocardiography, multiple gated radionuclide angiography, quantitative gated blood-pool SPECT, (123)I-metaiodobenzylguanidine scintigraphy, or cardiac magnetic resonance imaging. These approaches differ from each other with regards to availability, accuracy, sensitivity to detect early stages of cardiac injury, individual reliability, ease of use in a longitudinal follow-up perspective, and to related cost-effectiveness. Improving prevention of these cardiac side-effects depends on several, currently unresolved issues. Early detection and quantification of cardiac damage is required to adapt chemotherapy in progress for optimal management of patients. Whether increased availability of myocardial strain imaging and repeat blood biomarkers determinations will reliably and consistently achieve these goals remain to be confirmed. Also, protective approaches to reduce cardiac toxicity of anticancer drugs should be reconsidered according to the recently restricted approval for use of dexrazoxane. Anthracycline-based regimens, encapsulated anthracyclines and non-anthracycline regimens should be revisited with regards to antitumour efficacy and cardiac toxicity. Cardiovascular drugs that proved effective in prevention of anthracycline-induced cardiac toxicity in experimental models should be investigated in clinical trials. Finally, the efficacy of cardiovascular drugs that have already been tested in clinical settings should be confirmed and compared with each other in patients in increased numbers.

Topics: Anthracyclines; Antineoplastic Agents; Antioxidants; Arrhythmias, Cardiac; Biomarkers; Cardiovascular Agents; Cytotoxins; Diagnostic Techniques, Cardiovascular; Heart Diseases; Heart Failure; Heart Function Tests; Humans; Liposomes; Molecular Targeted Therapy; Myocardial Ischemia; Natriuretic Peptides; Neoplasms; Protein Kinase Inhibitors; Troponin; Ventricular Dysfunction, Left

Topics: Anti-Infective Agents; Antineoplastic Agents; Aromatase Inhibitors; Cardiovascular Agents; Clopidogrel; Genome-Wide Association Study; Genomics; Genotype; Humans; Neoplasms; Pharmacogenetics; Polymorphism, Genetic; Ticlopidine; Warfarin

The unique clinical circumstances that are typically encountered by cardiology providers when caring for patients undergoing treatment for cancer require an in-depth understanding of the recommended treatments for the diagnosis and management of heart failure and ischemic heart disease. It is also recognized that there is not a broadly described clinical research basis from which to provide guidance when specific clinical decision making is required. Thus, it is imperative that cardiology and oncology closely collaborate when difficult patient decisions arise. Engaging each discipline together with active patient involvement in clinical care will undoubtedly provide optimal care for our patients.

Topics: Aged; Antineoplastic Agents; Cardiology; Cardiovascular Agents; Cardiovascular Diseases; Comprehensive Health Care; Drug Interactions; Evidence-Based Medicine; Female; Humans; Interdisciplinary Communication; Male; Medical Oncology; Middle Aged; Monitoring, Physiologic; Neoplasms; Patient Selection; Risk Assessment

Cardiovascular disease and cancer are 2 of the leading causes of death globally. Certain cardiovascular medications have been linked to an increased risk for cancer. Although individual reviews of specific classes of cardiovascular medications have been published previously, a more complete review of several classes has not been performed. The aim of this review is to evaluate the associations of various cardiovascular agents with the risk for developing cancer and provide guidance for clinicians. A comprehensive search of published research was conducted using MEDLINE from 1994 to 2011. Three trials demonstrated an increased risk for cancer using angiotensin II receptor blockers. Additionally, risk for cancer was shown in a number of trials that included the use of angiotensin II receptor blockers in combination with angiotensin-converting enzyme inhibitors. Five trials suggested that diuretics increased the risk for specific cancers, especially in women and those who had been using diuretics for >4 years. Statins and ezetimibe, in contrast, did not show this increased risk. Prasugrel was shown to be associated with an increased risk for cancer in 1 study. It appears that the use of certain cardiovascular medications is associated with an increased risk for cancer. In conclusion, clinicians need to balance the risks and benefits of the use of these agents and provide the appropriate therapy on an individual basis.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Global Health; Humans; Incidence; Neoplasms; Risk Factors

The therapeutic areas of infectious diseases and oncology have benefited from abundant scaffold diversity in natural products, able to interact with many specific targets within the cell and indeed for many years have been source or inspiration for the majority of FDA approved drugs. The present review describes natural products (NPs), semi-synthetic NPs and NP-derived compounds that have undergone clinical evaluation or registration from 2005 to 2010 by disease area i.e. infectious (bacterial, fungal, parasitic and viral), immunological, cardiovascular, neurological, inflammatory and related diseases and oncology.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Biological Products; Cardiovascular Agents; Cardiovascular Diseases; Communicable Diseases; Drug Discovery; Humans; Inflammation; Metabolic Diseases; Neoplasms; Nervous System Diseases; Plant Extracts; Plants, Medicinal

Cancer treatment has improved extraordinarily in recent years. The development of targeted therapies has widened the cardiotoxic spectrum of antineoplastic drugs. Optimum management of cardiovascular disease before and during antineoplastic treatment is essential to reduce morbidity and mortality in cancer patients. This article reviews the incidence and characteristics of cardiotoxic effects of antineoplastic drugs with special focus on the pathophysiological mechanisms. It also emphasizes the importance of early detection and correction of cardiovascular risk factors and the relevance of close cardiac monitoring during antineoplastic treatment in order to reduce cardiotoxicity.

Topics: Antineoplastic Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Heart Diseases; Humans; Incidence; Ischemia; Molecular Targeted Therapy; Neoplasms; Ventricular Dysfunction, Left

Several studies have cited the Mediterranean diet as an example of healthy eating. In fact, the Mediterranean diet has become the reference diet for the prevention of cardiovascular disease. Red wine seems to be an essential component of the diet, since moderate consumption of wine is associated with lower risk and mortality from cardiovascular disease. Evidence is also accumulating that wine helps prevent the development of certain cancers. Of all the many components of wine, resveratrol, which is a natural component specifically present in wine, has been identified as being mainly responsible for these health-promoting properties. Many valuable properties such as cardioprotective and anticarcinogenic activity have been attributed to resveratrol; however, its bioavailability is quite low. The bioactivity of metabolites derived from resveratrol, and the accumulation of resveratrol in vital organs are still under study, but there are high expectations of positive results. Other stilbene compounds are also considered in this review, despite being present in undetectable or very small quantities in wine. The present paper reviews all aspects of the health properties of wine, bioactive compounds found in wine, and their concentrations, bioavailability and possible synergistic effects.

Topics: Anticoagulants; Antineoplastic Agents, Phytogenic; Biological Availability; Cardiovascular Agents; Diet, Mediterranean; Humans; Lipid Metabolism; Neoplasms; Protective Agents; Resveratrol; Stilbenes; Vitis; Wine

Topics: Animals; Antineoplastic Agents; Biomedical Research; Cachexia; Cardiovascular Agents; Cardiovascular Diseases; Drug Design; Genetic Therapy; Humans; Mice; MicroRNAs; Muscle, Skeletal; Neoplasms; Proteasome Endopeptidase Complex; Telomere; Ubiquitin; Ubiquitination

Medical disease and the methods used to treat disease that can result in sexual problems. The prevalence and pathophysiology of sexual dysfunction have been prominent questions in medicine for more than a decade. Pertinent information related to sexual dysfunction and medical illness, with special emphasis on cardiovascular health, endocrine-related disorders, and malignancy are presented.

Topics: Antineoplastic Agents; Body Image; Cardiovascular Agents; Cardiovascular Diseases; Chronic Disease; Diabetes Complications; Female; Hormones; Humans; Hysterectomy; Mastectomy, Segmental; Metabolic Syndrome; Neoplasms; Physician-Patient Relations; Radiotherapy; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological

Molecular imaging biomarkers are playing an increasingly important role in efforts to increase the probability of success of drug candidates by helping to validate novel drug targets in support of proof-of-concept testing early in the drug discovery and development process. By facilitating better and faster decision-making, molecule and mechanism-based failures can be identified and eliminated from a research portfolio early in development thereby focusing research efforts on the best drug candidates and therapeutic hypotheses. Molecular imaging can be used to improve the cost-effectiveness of studying unprecedented mechanisms, decrease cycle time, and improve drug pipeline quality.

Topics: Animals; Antineoplastic Agents; Atherosclerosis; Biomarkers, Pharmacological; Cardiovascular Agents; Central Nervous System Agents; Diagnostic Imaging; Drug Design; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Neoplasms; Optics and Photonics; Patient Selection; Positron-Emission Tomography; Technology, Pharmaceutical; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography

Unlike other CDKs, CDK9 does not regulate the cell cycle but promotes RNA synthesis in genetic programmes for cell growth, differentiation and viral pathogenesis. It is becoming clear that CDK9 inhibition contributes to the anticancer activity of most CDK inhibitors under clinic investigation. CDK9 was discovered in the context of HIV research because retroviruses hijack host transcription and CDK9 inhibitors might become specific antiretroviral agents, particularly as they might prevent drug resistance. Myocardial hypertrophy is a risk factor in congestive heart failure and is characterised by derepressed CDK9 activity. CDK9 inhibitors, thus, can find therapeutic application in cardiology. Although there are strong signs that CDK9 inhibition would be a useful therapeutic strategy in all three indications, the lack of selective inhibitors has so far confounded clinical development. Here we give an overview of the validity of CDK9 as a drug target and of the current knowledge of this kinase and its inhibitors.

Topics: Animals; Antineoplastic Agents; Antiviral Agents; Cardiovascular Agents; Cyclin-Dependent Kinase 9; Drug Delivery Systems; Heart Diseases; Humans; Neoplasms; Virus Diseases

The NIH Pharmacogenetics Research Network (PGRN) is a collaborative group of investigators with a wide range of research interests, but all attempting to correlate drug response with genetic variation. Several research groups concentrate on drugs used to treat specific medical disorders (asthma, depression, cardiovascular disease, addiction of nicotine, and cancer), whereas others are focused on specific groups of proteins that interact with drugs (membrane transporters and phase II drug-metabolizing enzymes). The diverse scientific information is stored and annotated in a publicly accessible knowledge base, the Pharmacogenetics and Pharmacogenomics Knowledge base (PharmGKB). This report highlights selected achievements and scientific approaches as well as hypotheses about future directions of each of the groups within the PGRN. Seven major topics are included: informatics (PharmGKB), cardiovascular, pulmonary, addiction, cancer, transport, and metabolism.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Carrier Proteins; Drug Therapy; Humans; Informatics; Lung Diseases; Neoplasms; Pharmaceutical Preparations; Pharmacogenetics; Platelet Aggregation Inhibitors; Polymorphism, Single Nucleotide; Substance-Related Disorders

Although effective anti-neoplastic agents, anthracyclines are limited by their well recognized and pervasive cardiotoxic effects. The incidence of late progressive cardiovascular disease in long-term survivors of cancer is established and may contribute to heart failure and death. To maximize the benefits of these drugs, a high-risk population has been identified and new strategies have been investigated to minimize toxic effects, including limiting the cumulative dose, controlling the rate of administration and using liposomal preparations and novel anthracycline analogues. Dexrazoxane also shows promise as a cardioprotectant during treatment. This paper reviews these strategies, as well as medications used to manage anthracycline-induced cardiotoxicity, and functional and biochemical means of monitoring cardiotoxicity, including echocardiography, radionuclide scans and biomarker analysis. The treatment of adult cancer survivors who have had anthracycline-related cardiotoxicity has not been systematically studied. Empirically, anthracycline-associated cardiac dysfunction is treated very similarly to other forms of heart failure. These treatments include avoiding additional cardiotoxic regimens, controlling hypertension, lifestyle changes, medications and heart transplantation.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Cardiovascular Agents; Drug Interactions; Drug Monitoring; Heart; Heart Diseases; Humans; Neoplasms; Razoxane; Risk Factors

Dexrazoxane is highly effective in reducing anthracycline-induced cardiotoxicity and extravasation injury and is used clinically for these indications. Dexrazoxane has two biological activities: it is a prodrug that is hydrolyzed to an iron chelating EDTA-type structure and it is also a strong inhibitor of topoisomerase II. Doxorubicin is able to be reductively activated to produce damaging reactive oxygen species. Iron-dependent cellular damage is thought to be responsible for its cardiotoxicity. The available experimental evidence supports the conclusion that dexrazoxane reduces doxorubicin cardiotoxicity by binding free iron and preventing site-specific oxidative stress on cardiac tissue. However, it cannot be ruled out that dexrazoxane may also be protective through its ability to inhibit topoisomerase II.

Topics: Animals; Antineoplastic Agents; Cardiovascular Agents; Clinical Trials as Topic; Doxorubicin; Enzyme Inhibitors; Heart Diseases; Humans; Neoplasms; Prodrugs; Razoxane; Topoisomerase II Inhibitors

This article discusses the use of nanotechnology in drug delivery approaches. Magnetic nanotechnology is finding wide applications in medicine, most notably in MRI and magnetic separation. The impedance biosensor is expected to find applications in monitoring cytokines in cancer, bone turnover markers in osteoporosis, and understanding neural-degenerative diseases.

Topics: Animals; Antineoplastic Agents; Cardiovascular Agents; Cardiovascular Diseases; Drug Carriers; Drug Delivery Systems; Humans; Nanomedicine; Nanostructures; Neoplasms

Resistance to anticancer drugs is often related to deficient cell death execution pathways in cancer cells. Apoptosis, which denotes a form of cell death executed by caspases, was traditionally considered as the only physiological and programmed form of cell death. However, recent evidence indicates that programmed cell death (PCD) can occur in complete absence of caspase activation. Indeed, a large number of caspase-independent models are now defined and a key protein implicated in this type of PCD, apoptosis-inducing factor (AIF), has been identified. AIF is a mitochondrial protein with two faces looking in opposite life/death directions. Recently, the identification of five different isoforms allowed a better characterization of AIFs life/mitochondrial versus death/nuclear functions, as well as definition of its pro-apoptotic region and some of its nuclear partners. Importantly, much work on caspase-independent PCD has revealed that AIF participates in more PCD systems than initially thought. A wider molecular knowledge of AIF, and of the caspase-independent PCDs in which it is involved, are key to provide new insights into the role of PCD. There is no doubt that these insights will lead to the development of more selective and efficient drugs against cancer, degenerative diseases, and other pathological disorders implicating AIF.

Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Apoptosis; Apoptosis Inducing Factor; Cardiovascular Agents; Caspases; Cell Nucleus; Drug Resistance, Neoplasm; Enzyme Activation; Humans; Ischemia; Mitochondria; Models, Molecular; Molecular Sequence Data; Neoplasms; Neurodegenerative Diseases; Neuroprotective Agents; Protein Conformation; Protein Isoforms

Statins are pluripotent agents exhibiting multiple non-lipid-lowering actions. Besides their established role in the management of hypercholesterolemia, statins may also have beneficial actions in other pathological conditions, namely: a) osteoporosis and osteoporosis-related bone fractures, b) cancer, c) solid organ transplantation, d) cerebrovascular events (transient ischemic attack and stroke episodes), e) various neurological disorders, such as Alzheimer's disease, Parkinson's disease and multiple sclerosis, f) cardiac arrhythmias and heart failure, g) renal diseases, h) rheumatoid arthritis, i) autoimmune diseases, j) sepsis, and k) allergic asthma. We reviewed the literature searching for studies that support or oppose the use of statins in each proposed indication. In some of these emerging indications, a role for statin treatment is more firmly set; for others, current evidence is more controversial. Future trials may reveal more convincing evidence that will make statin use necessary in the therapeutic management of several diseases.

Topics: Animals; Anti-Asthmatic Agents; Antineoplastic Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Asthma; Autoimmune Diseases; Bone Density Conservation Agents; Cardiovascular Agents; Cerebrovascular Disorders; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Neoplasms; Nervous System Diseases; Neuroprotective Agents; Organ Transplantation; Osteoporosis; Sepsis

The nthracycline antibiotics are among the most widely used and effective anticancer drugs. The therapeutic efficacy of this class of drugs is limited by cumulative cardiac toxicity. Dexrazoxane is the only clinically approved cardioprotective agent used in anthracycline-containing anticancer therapy. Its cardioprotective action allows the use of a much higher cumulative dose of anthracyclines and improvement in the effectiveness of treatment. Anthracyclines form complexes with iron ions, which are very active in the production of reactive oxygen species responsible for the lipid peroxidation of mitochondrial and endoplasmatic reticulum membranes. This process seems to be the major cause of anthracycline-induced cardiotoxicity. Dexrazoxane exerts its protective effects by rapid and complete binding of ferric and ferrous ions, even by displacing the metal ions from complexes with anthracyclines. Besides its cardioprotective effect, dexrazoxane also exhibits anticancer properties. Like other derivatives of bisdioxopiperazine, dexrazoxane is a catalytic inhibitor of eukaryotic DNA topoisomerase II, the key enzyme controlling DNA topology and contributing to the replication and transcription processes. Dexrazoxane is able to lock topoisomerase II at the stage of the enzyme reaction cycle where the enzyme forms a closed clamp around the DNA. This phenomenon seems to be the main reason for the generation of DNA double-strand breaks by dexrazoxane as well as its cytotoxicity against quickly proliferating cancer cells. Other effects of its topoisomerase II catalytic inhibition is the induction of cell differentiation and apoptosis. Dexrazoxane may be used not only as a cardioprotective agent, but also as a modulator of action of some anticancer drugs by enhancing their selectivity or by delaying the development of multidrug resistance.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Chelating Agents; Neoplasms; Razoxane

Anthracyclines play a major role in chemotherapeutic regimens for a variety of childhood cancers, but produce dose-related cardiotoxicity. Dexrazoxane, a chelating agent that binds iron intracellularly, has been cautiously included in anthracycline-based regimens. Our understanding of anthracycline and dexrazoxane pharmacokinetics in children is very limited. In addition, the administration schedule used for adults (bolus dexrazoxane prior to bolus anthracycline) may not be the best to attain both short- and long-term cardioprotection. Dexrazoxane could diminish the anti-tumor activity of and/or increase toxicities from anthracyclines. Pediatric oncologists must be assured this intervention does not diminish the success in curing children with cancer.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Child; Humans; Neoplasms; Razoxane

Adverse drug-drug interactions are a major cause of morbidity and mortality. Cancer patients are at particularly high risk of such interactions because they commonly receive multiple medications, including cytotoxic chemotherapy, hormonal agents and supportive care drugs. In addition, the majority of cancer patients are elderly, and so require medications for co-morbid conditions such as cardiovascular, gastrointestinal, and rheumatological diseases. Furthermore, the age-related decline in hepatic and renal function reduces their ability to metabolize and clear drugs and so increases the potential for toxicity. Not all drug-drug interactions can be predicted, and those that are predictable are not always avoidable. However, increased awareness of the potential for these interactions will allow healthcare providers to minimize the risk by choosing appropriate drugs and also by monitoring for signs of interaction. This review considers the basic principles of drug-drug interactions, and presents specific examples that are relevant to oncology.

Topics: Anti-Infective Agents; Antineoplastic Agents; Bronchodilator Agents; Cardiovascular Agents; Comorbidity; Contraindications; Drug Interactions; Gastrointestinal Agents; Humans; Neoplasms; Psychotropic Drugs

Dexrazoxane (Cardioxane, Zinecard, a cyclic derivative of edetic acid, is a site-specific cardioprotective agent that effectively protects against anthracycline-induced cardiac toxicity. Dexrazoxane is approved in the US and some European countries for cardioprotection in women with advanced and/or metastatic breast cancer receiving doxorubicin; in other countries dexrazoxane is approved for use in a wider range of patients with advanced cancer receiving anthracyclines. As shown in clinical trials, intravenous dexrazoxane significantly reduces the incidence of anthracycline-induced congestive heart failure (CHF) and adverse cardiac events in women with advanced breast cancer or adults with soft tissue sarcomas or small-cell lung cancer, regardless of whether the drug is given before the first dose of anthracycline or the administration is delayed until cumulative doxorubicin dose is > or =300 mg/m2. The drug also appears to offer cardioprotection irrespective of pre-existing cardiac risk factors. Importantly, the antitumour efficacy of anthracyclines is unlikely to be altered by dexrazoxane use, although the drug has not been shown to improve progression-free and overall patient survival. At present, the cardioprotective efficacy of dexrazoxane in patients with childhood malignancies is supported by limited data. The drug is generally well tolerated and has a tolerability profile similar to that of placebo in cancer patients undergoing anthracycline-based chemotherapy, with the exception of a higher incidence of severe leukopenia (78% vs 68%; p < 0.01). Dexrazoxane is the only cardioprotective agent with proven efficacy in cancer patients receiving anthracycline chemotherapy and is a valuable option for the prevention of cardiotoxicity in this patient population.

Topics: Anthracyclines; Antineoplastic Agents; Cardiovascular Agents; Cardiovascular Diseases; Humans; Neoplasms; Randomized Controlled Trials as Topic; Razoxane

Cardiac toxicity due to anti-neoplastic agents has been recognized since doxorubicin, one of the most effective anthracyclines, was introduced in the early 1970s. Although the frequency of cardiac toxicity is relatively low compared with hematological and gastrointestinal toxicity, management of cardiac toxicity is crucial because of the possibility of irreversible cardiac damage. Recently, high dose-intense chemotherapy with G-CSF and stem cell transplantation, and mediastinal irradiation, produce even more toxic effects on the heart. This review describes some of the cardiac toxicity of anthracyclines and trastuzumab, and discusses attempts at management. The mainstay of management of cardiac toxicity is serial, adequate monitoring of cardiac functions.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Agents; Dose-Response Relationship, Drug; Doxorubicin; Echocardiography; Heart; Heart Diseases; Humans; Monitoring, Physiologic; Neoplasms; Razoxane

The aim of this article is to review (based on the literature data) the mechanism of chemotherapy- and radiation-induced cardiac toxicity, diagnostic procedures and methods of reducing this toxicity. Cardiac toxicity associated with chemotherapy and radiotherapy may be life threatening, can limit the dose and duration of the treatment and certainly adversely affect short-term and long-term quality of life. A development of new strategies for reduction and prophylaxis of cardiac toxicity has great clinical impact. Chemotherapeutic agents may cause acute myocardial injury or chronic complications (e.g. congestive heart failure). Among cardiotoxic agents anthracyclines cause most serious cumulative, dose-limiting and dose-related cardiomyopathy. Most of them are subclinical changes, however studies demonstrate that symptomatic congestive heart failure in 6-10% of adults who received a cumulative, bolus doses of 550 mg/m2. The frequency of cardiomyopathy may be reduced by modifying the schedule of administration, patients selection considering risk factors, careful cardiac monitoring during chemotherapy, using less toxic doxorubicin analogues and liposomal formulation. The use of pharmacological protection with dexrazoxane remains controversial. A substantial risk of cardiotoxicity may be associated with radiotherapy of the chest and mediastinum. Moreover, radiotherapy may have an additive affect to chemotherapy-induced toxicity. However, with the use of modern treatment techniques radiation cardiomyopathy is uncommon. A group of patients at risk of cardiac complication are patients with breast cancer, Hodgkin's and non-Hodgkin's lymphomas and soft tissue sarcomas.

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Cardiomyopathy, Dilated; Cardiovascular Agents; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Female; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Neoplasms; Radiotherapy, Adjuvant; Razoxane; Risk Factors; Sarcoma

Dexrazoxane has been used successfully to reduce cardiac toxicity in patients receiving anthracycline-based chemotherapy for cancer (predominantly women with advanced breast cancer). The drug is thought to reduce the cardiotoxic effects of anthracyclines by binding to free and bound iron, thereby reducing the formation of anthracycline-iron complexes and the subsequent generation of reactive oxygen species which are toxic to surrounding cardiac tissue. Clinical trials in women with advanced breast cancer have found that patients given dexrazoxane (about 30 minutes prior to anthracycline therapy; dexrazoxane to doxorubicin dosage ratio 20:1 or 10:1) have a significantly lower overall incidence of cardiac events than placebo recipients (14 or 15% vs 31%) when the drug is initiated at the same time as doxorubicin. Cardiac events included congestive heart failure (CHF), a significant reduction in left ventricular ejection fraction and/or a > or = 2-point increase in the Billingham biopsy score. These results are supported by the findings of studies which used control groups (patients who received only chemotherapy) for comparison. The drug appears to offer cardiac protection irrespective of pre-existing cardiac risk factors. In addition, cardiac protection has been shown in patients given the drug after receiving a cumulative doxorubicin dose > or = 300 mg/m2. It remains to be confirmed that dexrazoxane does not affect the antitumour activity of doxorubicin: although most studies found that clinical end-points (including tumour response rates, time to disease progression and survival duration) did not differ significantly between treatment groups, the largest study did show a significant reduction in response rates in dexrazoxane versus placebo recipients. Dexrazoxane permits the administration of doxorubicin beyond standard cumulative doses; however, it is unclear whether this will translate into prolonged survival. Preliminary results (from small nonblind studies) indicate that dexrazoxane reduces cardiac toxicity in children and adolescents receiving anthracycline-based therapy for a range of malignancies. The long term benefits with regard to prevention of late-onset cardiac toxicity remain unclear. With the exception of severe leucopenia [Eastern Cooperative Oncology Group (ECOG) grade 3/4 toxicity], the incidence of haematological and nonhaematological adverse events appears similar in patients given dexrazoxane to that in placebo recipients undergoing. Dexrazoxane is a valuable drug for protecting against cardiac toxicity in patients receiving anthracycline-based chemotherapy. Whether it offers protection against late-onset cardiac toxicity in patients who received anthracycline-based chemotherapy in childhood or adolescence remains to be determined. Further clinical experience is required to confirm that it does not adversely affect clinical outcome, that it is a cost-effective option, and to determine the optimal treatment regimen.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Cardiovascular Agents; Chelating Agents; Heart Diseases; Humans; Neoplasms; Razoxane

The dose-limiting toxicity of the widely used anticancer agent, doxorubicin, is a destructive, irreversible and progressive cardiomyopathy. Prevention of this cardiotoxicity without reduction of antitumour efficacy or the production of new toxicities has therefore been a long-time therapeutic goal. It has now been largely achieved by prior administration of dexrazoxane (DXRz; Cardioxane in Europe; Zinecard in North America; ICRF 187). Six randomized, controlled clinical trials in breast and lung cancer and in soft tissue sarcomas of children have shown a 90% reduction in doxorubicin-induced cardiotoxicity. The results of all these trials lead to the conclusion that DXRz permits: (1) cardiotoxic doses of doxorubicin to be given without cardiotoxicity; (2) patients with increased cardiac risk factors to be treated with full doses of dioxorubicin; (3) second-line treatment with other cardiotoxic drugs.

Topics: Adult; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Doxorubicin; Female; Humans; Male; Neoplasms; Razoxane; Treatment Outcome

Chemotherapy drugs have been reported to cause cardiac side effects including cardiomyopathy, ischemia, arrhythmias, and myocardial necrosis. Most important in terms of daily practice is anthracycline-induced cardiomyopathy. The bisdioxopiperazine compound, dexrazoxane (ICRF-187, ADR-529), has been shown to prevent this cumulative side effect of the anthracyclines. Recent randomized trials performed in breast cancer and in pediatric sarcoma patients have demonstrated the efficacy of this approach, which permits the administration of anthracyclines to greater cumulative doses and thus leads to a substantial reduction in the incidence of decreased left-ventricular ejection fraction or congestive heart failure. Response rates were not significantly different with the use of dexrazoxane in these trials. The risk ratio for a cardiac event was decreased by two to threefold in randomized breast studies involving more than 700 women. Paclitaxel also has been reported to cause arrhythmias and possibly ischemia. In a large data base, National Cancer Institute investigators found a 0.29% incidence of grade 4 or 5 cardiac toxicities, including heart block, ventricular tachycardia, and ischemic events. Other important chemotherapy-related cardiac toxicities discussed include fluorouracil-induced angina and arrhythmias, interleukin-4 induced-cardiomyopathy, and cardiotoxicity associated with autologous bone marrow transplantation procedures.

Topics: Adult; Anthracyclines; Antineoplastic Agents; Cardiovascular Agents; Child; Clinical Trials as Topic; Cyclophosphamide; Female; Fluorouracil; Heart; Heart Diseases; Humans; Interleukin-2; Male; Neoplasms; Paclitaxel; Razoxane; Retrospective Studies; Survivors

Topics: Analgesics; Animals; Anticholesteremic Agents; Bacteria; Cardiovascular Agents; Drug Evaluation, Preclinical; Humans; Hyperglycemia; Neoplasms; Protease Inhibitors

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; Cardiovascular Agents; Hodgkin Disease; Humans; Leukemia; Neoplasms

To determine the recommended phase II dose and evaluate the safety and toxicity profile and pharmacokinetic (PK) and pharmacodynamic (PD) effects of BNC105P, an inhibitor of tubulin polymerization that has vascular disrupting and antiproliferative effects.. BNC105P was administered as a 10-minute infusion on days 1 and 8 of a 21-day cycle in a first-in-human phase I study. A dynamic accelerated dose titration method was used for dose escalation. Plasma concentrations of BNC105P (phosphate prodrug) and BNC105 (active agent) were determined. PD assessments were carried out using dynamic contrast enhanced (DCE)-MRI and analysis of a blood-borne biomarker.. Twenty-one subjects with advanced solid tumors were enrolled on 6 dose levels (range: 2.1-18.9 mg/m(2)). The recommended dose level was 16 mg/m(2) and was well tolerated. BNC105P (prodrug) rapidly converted to BNC105 with a half-life of 0.13 hours. Plasma concentrations of BNC105 generally increased in proportion to dose with a half-life of 0.57 hours. Pharmacodymanically active plasma levels were obtained with a dose dependant reduction in the levels of polymerized tubulin (on-target action) being observed in PBMCs. DCE-MRI also indicated blood flow changes in the tumor lesions of a number of subjects.. BNC105P has a favorable toxicity profile at the recommended dose of 16 mg/m(2) and is associated with PD changes consistent with its known mechanism of action. Phase II studies in renal cancer and mesothelioma have commenced.

Topics: Adult; Aged; Aged, 80 and over; Anisoles; Antineoplastic Agents; Benzofurans; Biomarkers; Cardiovascular Agents; Cell Proliferation; Female; Humans; Male; Middle Aged; Neoplasms; Organophosphates; Prodrugs; Tubulin

This study attempted to assess the incidence and outcome of anthracycline cardiotoxicity and the role of dexrazoxane as a cardioprotectant in childhood solid tumors. The dexrazoxane group included 47 patients and the control group of historical cohort included 42. Dexrazoxane was given in the 10:1 ratio to doxorubicin. Fractional shortening and systolic and diastolic left ventricular diameters were used to assess the cardiac function. The median follow-ups were 54 months in the dexrazoxane group and 86 months in the control group. The mean cumulative doses of doxorubicin were 280.8+/-83.4 mg/m(2) in the dexrazoxane group and 266.1+/-75.0 mg/m(2) in the control group. The dexrazoxane group experienced significantly fewer cardiac events (27.7% vs. 52.4%) and less severe congestive heart failure (6.4% vs. 14.3%) than the control group. Thirteen cardiotoxicities including one cardiac death and 2 congestive heart failures occurred in the dexrazoxane group, and 22 cardiotoxicities including 2 cardiac deaths and 4 congestive heart failures, in the control group. Five year cardiac event free survival rates were 69.2% in the dexrazoxane group and 45.8% in the control group (P=0.04). Dexrazoxane reduces the incidence and severity of early and late anthracycline cardiotoxicity in childhood solid tumors.

Topics: Adolescent; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Child; Child, Preschool; Cohort Studies; Disease-Free Survival; Doxorubicin; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Infant; Male; Neoplasms; Razoxane; Ventricular Function, Left

We sought to investigate the long-term efficacy of oral sirolimus therapy and its impact on the incidence of de novo malignancies in the OSIRIS (Oral Sirolimus to Inhibit Recurrent In-Stent Stenosis) trial population.. The OSIRIS trial showed a significant reduction of angiographic restenosis with an oral adjunctive sirolimus treatment for in-stent restenosis. The long-term efficacy of oral sirolimus therapy is unknown.. Three hundred patients with in-stent restenosis were randomly assigned to receive placebo, a cumulative loading dose of 8 mg (usual-dose), or 24 mg (high-dose) of sirolimus over 3 days (2 days before and the day of intervention) followed by maintenance therapy of 2 mg/day for 7 days. The primary outcome of this analysis was the incidence of composite of death, myocardial infarction, and target vessel revascularization at 4-year follow-up. Secondary outcome was the incidence of newly diagnosed malignancies.. No significant differences were observed between placebo, usual-, and high-dose sirolimus treatment groups regarding primary outcome (33.3%, 39.4%, and 31.3%, respectively; p = 0.46), death (5.9%, 9.1%, and 11.1%, respectively; p = 0.41), target vessel revascularization (30.4%, 30.3%, and 22.2%, respectively; p = 0.33), and rate of newly diagnosed malignancies (7.8%, 3.0%, and 11.1%, respectively; p = 0.09).. The benefit in the reduced need for repeat intervention observed at 1 year with high-dose oral sirolimus therapy was attenuated over 4 years. Moreover, this regimen was associated with numerical yet not a significant increase in newly diagnosed malignancies without augmenting the malignancy-induced risk of death. (Oral Sirolimus for In-Stent Restenosis [OSIRUS] trial; NCT00859183).

Topics: Administration, Oral; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Double-Blind Method; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Middle Aged; Myocardial Infarction; Neoplasms; Risk Assessment; Sirolimus; Time Factors

The authors conducted an 8-year prospective non-randomised study to determine whether dexrazoxane (ICRF-187) would reduce late anthracycline-induced cardiotoxicity in patients treated in childhood for haematological malignancy. The authors examined prospectively 75 patients (40 male/35 female) aged 2-17 years (median 6.5 years) at the time of diagnosis. The cardioprotection was given to 53 patients (26 male/17 female) and the standard protocol was used in 22 patients (14 male/8 female). The prospective echocardiographic evaluation was done before and after the chemotherapy and every year during the follow-up period. Dynamic stress echocardiography (DSE) was assessed in the final year. The clinical cardiotoxicity was not diagnosed. Higher cumulative doses of anthracycline were given in the dexrazoxane group (234+/-58 mg/m(2), median 240 mg/m(2) versus 203+/-86 mg/m(2), median 210 mg/m(2), P <0.04) and a significantly higher percentage of patients received cumulative doses >240 mg/m(2) of anthracycline ( P <0.05). During the follow-up period, the fractional shortening (FS) declined in the no-dexrazoxane group only in the 8th year and was significantly lower compared to the dexrazoxane group ( P <0.05). The pathological decrease in FS was present in 24% of patients; 41% in the no-dexrazoxane and 17% in the dexrazoxane groups, respectively ( P <0.05). DSE demonstrated lower rest EF and cardiac index (CI) in the no-dexrazoxane group ( P <0.05); however, neither the response of EF and CI to the stress echocardiography nor the exercise tolerance significantly differed between sub-groups. A higher number of patients in the dexrazoxane group had very good exercise tolerance (ET) >3 Watts/kg ( P <0.05) and a lower number responded with a decreased ET <2 Watts/kg ( P <0.05) compared to the no-dexrazoxane group.. Dexrazoxane seems to reduce the risk of late subclinical cardiotoxicity. Dexrazoxane-treated patients revealed better exercise tolerance; however the haemodynamic response to the stress was no different in both sub-groups.

Topics: Adolescent; Anthracyclines; Antineoplastic Agents; Blood Pressure; Body Mass Index; Cardiovascular Agents; Child; Child, Preschool; Czech Republic; Daunorubicin; Dose-Response Relationship, Drug; Doxorubicin; Echocardiography, Stress; Female; Follow-Up Studies; Heart; Heart Rate; Humans; Infant; Male; Neoplasms; Prospective Studies; Razoxane; Time Factors; Treatment Outcome

Dexrazoxane administration prior to short infusion doxorubicin prevents anthracycline-related heart damage. Since delivery of doxorubicin by 96-h continuous intravenous infusion also reduces cardiac injury, we studied delivering dexrazoxane and doxorubicin concomitantly by prolonged intravenous infusion.. Patients with advanced malignancies received tandem cycles of concurrent 96-h infusions of dexrazoxane 500 mg/m2 and doxorubicin 165 mg/m2, and 24 h after completion of chemotherapy, granulocyte-colony stimulating factor (5 microg/kg) and oral levofloxacin (500 mg) were administered daily until the white blood cell count reached 10,000 microl(-1). Plasma samples were analyzed for dexrazoxane and doxorubicin concentrations.. Ten patients were enrolled; eight patients had measurable disease. Two partial responses were observed in patients with soft-tissue sarcoma. The median number of days of granulocytopenia (<500 microl(-1)) was nine and of platelet count <20,000 microl(-1) was seven. Six patients received a single cycle because of progression (one), stable disease (four), or reversible, asymptomatic 10% decrease in cardiac ejection fraction (two). Principal grade 3/4 toxicities included hypotension (two), anorexia (four), stomatitis (four), typhlitis (two), and febrile neutropenia (seven), with documented infection (three). One death from neutropenic sepsis occurred. Dexrazoxane levels ranged from 1270 to 2800 nM, and doxorubicin levels ranged from 59.1 to 106.9 nM.. These results suggest that tandem cycles of concurrent 96-h infusions of dexrazoxane and high-dose doxorubicin can be administered with minimal cardiac toxicity, and have activity in patients with recurrent sarcomas. However, significant non-cardiac toxicities indicate that the cardiac sparing potential of this approach would be maximized at lower dose levels of doxorubicin.

Topics: Adult; Antibiotics, Antineoplastic; Cardiovascular Agents; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Granulocyte Colony-Stimulating Factor; Heart Failure; Humans; Infusions, Intravenous; Levofloxacin; Male; Middle Aged; Neoplasms; Neutropenia; Ofloxacin; Razoxane; Sarcoma; Sepsis; Treatment Outcome

Everolimus-induced diabetes mellitus (DM) outcomes include everolimus-resistant tumors and poor hyperglycemia outcomes, which lead to various other negative clinical outcomes. This study aimed to evaluate the effect of associations between concomitant drug treatment and time to DM event occurrence (onset or exacerbation) on the outcomes of everolimus-induced DM in patients with cancer.. Data from the Japanese Adverse Drug Event Report database (JADER) were used, and patient drug use, time of DM event occurrence, and DM outcomes were determined from patient records. Associations between concomitant drug groups with everolimus and DM event occurrence were then evaluated for patients with both good and poor DM outcomes.. Top ten groups used concomitantly were drugs for the treatment of hypertension (HT), controlled DM, constipation, hypothyroidism, kidney disease, insomnia, hyperlipidemia, hyperuricemia, anemia, and gastritis. Among them, only HT, controlled DM, and hyperlipidemia were associated with DM event occurrence. These three drug groups were examined by the outcome of everolimus concomitant usage and revealed a significantly shorter time to DM event occurrence for patients with poor outcomes than for those with good outcomes (p = 0.015) among patients without a concomitant drug for DM. Each of these three drug groups was analyzed on patients who were concomitantly administered with one of each drug group with everolimus and revealed a significantly shorter time to DM event occurrence for patients with poor outcomes than for those with good outcomes in patients who received concomitant HT drugs (p = 0.006). Moreover, among the four HT drug categories, calcium channel blockers were significantly associated with poor outcomes (odds ratio, 2.18 [1.09-4.34], p = 0.028).. To prevent everolimus-induced poor DM outcomes, early DM detection and treatment are necessary, and the effect of the concomitant drug should be considered before initiating everolimus treatment.

Topics: Cardiovascular Agents; Diabetes Mellitus; Everolimus; Humans; Hyperlipidemias; Neoplasms

We investigated drugs that could sensitize KBV20C cancer cells resistant to eribulin or vincristine (VIC) treatment and assessed their associated mechanisms of action.. Such cancer cells were known to overexpress P-glycoprotein (P-gp). Considering that reserpine (P-gp inhibitor) plays a regulatory role in patients with high blood pressure, we investigated the effect of low doses of 27 blood pressure-regulating drugs on VIC-resistant KBV20C cells. This was done to identify drugs that could be repurposed for sensitizing antimitotic drug-resistant KBV20C cells at relatively low doses. Fluorescence-activated cell sorting (FACS), annexin V analyses, rhodamine uptake tests and western-blot analysis were performed to further investigate the mechanism of action of such drugs.. We found that co-treatment with amiodarone, nicardipine, carvedilol, or vardenafil at low doses could highly sensitize KBV20C cells treated with eribulin or VIC. These drugs reduced cellular viability, increased G. Highly antimitotic drug-resistant KBV20C cells can be sensitized by co-treatment with the repurposed blood pressure-regulating drugs amiodarone, nicardipine, carvedilol or vardenafil. These findings indicate that the repurposed blood pressure-regulating drugs may potentially be used in drug-resistant cancer patients without any toxic effects due to P-gp inhibition.

Topics: Blood Pressure; Cardiovascular Agents; Humans; Neoplasms

After enhancing the survivorship of cancers, the impact of cardiovascular diseases on mortality is increasing among cancer patients. However, anticancer therapies pose a higher cardiovascular risk to patients. As prevention against cancer therapy-induced cardiomyopathy has yet to be explored, the preventive ability of concomitant cardiovascular medications against incident heart failure was assessed.. A retrospective, population-based study was run using anonymized integration of healthcare databases. All the Hungarian patients diagnosed with breast or colorectal carcinoma and undergoing chemotherapy or biological therapy were analysed. Participants were not treated with any anticancer therapy nor suffered from heart failure/dilated cardiomyopathy during the preceding observational period (≥6.5 years). The heart failure endpoint was established by I50 International Classification of Diseases codes upon discharge from hospital or issuance of an autopsy report.. Among the 9575 patients who were enrolled, the cumulative incidence of heart failure over 4 years was 6.9%. The time until the first heart failure event in the propensity score-matched treated and untreated groups was compared using Cox proportional-hazards models. A significant association between lower heart failure risk and concomitant statin therapy was observed (hazard ratio: 0.748, P = 0.038); the preventive ability was more pronounced in the anthracycline/capecitabine/platinum-treated subgroup (hazard ratio: 0.660, P = 0.032). For angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapy, a significantly lower heart failure risk was also observed (hazard ratio: 0.809, P = 0.032). Among beta blockers, nebivolol administered to anthracycline/capecitabine-treated patients was associated with a nonsignificant trend to lower heart failure risk (hazard ratio: 0.584, P = 0.069).. Only concomitant statin and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapies were associated with significantly lower risk of anticancer therapy-related heart failure.

Topics: Antineoplastic Agents; Cardiomyopathies; Cardiotoxicity; Cardiovascular Agents; Databases, Factual; Female; Heart Failure; Humans; Hungary; Incidence; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Protective Factors; Retrospective Studies; Risk Adjustment

Cancer and cardiovascular disease are the 2 leading causes of death in most developed countries, making up the majority of national health care expenditures. In this study, we investigated nationwide trends of cardiovascular disease and cancer drug expenditure in relation to concomitant trends in cardiovascular disease and cancer death rates.. We obtained cardiovascular and cancer drug expenditure data in Denmark through the Danish Register of Medical Product Statistics. Trends in cancer deaths and cardiovascular disease deaths were observed by linkage to the cancer statistics for the Nordic Countries and Danish Heart Foundation databases.. Our data show that introduction and rapid uptake of generic versions of most cardiovascular disease drugs have resulted in a remarkable cost-neutral development in cardiovascular disease drug expenditure from 1995 to 2018 despite increased drug use. This development is contrasted to cancer drug expenditure, which has increased more than 15-fold in the same period. Since 2006, expenditure for cancer drugs has exceeded that for cardiovascular disease drugs and is now more than triple that cost. However, death rates for cancer have dropped a fraction as much as for cardiovascular disease.. Our results point to a disproportionate high mortality-adjusted expenditure for cancer drugs compared to cardiovascular disease drugs and demonstrate an enormous potential for national health care savings when cheaper versions like biosimilars of many cancer drugs are introduced.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biosimilar Pharmaceuticals; Cardiovascular Agents; Cardiovascular Diseases; Denmark; Drugs, Generic; Female; Health Expenditures; Health Policy; Humans; Male; Middle Aged; Mortality; Neoplasms

Current precision medicine approaches offer powerful tools to optimize medication regimens; however, the potential impact of these tools in cancer patients with multiple drug treatments has not fully appreciated yet. Here we describe a planning project scheduled to start in the next six months.. The overall endpoint of this project is to explore the potential association between the presence of individual genetic profile and severe toxicity rates in so-called "frail" cancer patients, using a nested case-control study design. The pilot study includes the detection of the individual pharmacogenetic profile of 150 (cases), prospect enrolled cancer "frail" patients, and 150 (control) retrospectively paired enrolled individuals. Methods for addressing the primary endpoint include: (a) Evaluation of cost-effectiveness analysis by recording QALY criteria; (b) Data recording by a brief self-administered questionnaire used to evaluate the adherence of a patient's tests and the impact of this genotyping on the patient's adverse drug reactions (ADR); (c) A sample size of paired (for age, gender, education, social status, geriatric syndromes, number of medications and comorbidities) 150 (cases) and 150 (controls); (d) Genotyping method choice by current widely diffuse platforms.. The investigators believe that genotype screening and the management of the overall cost of health care personalized therapy has the potential to reduce the health care costs of the Italian national health system (SSN).. Finally, the innovative issue of this project is to advocate the creation of a new model of the co-operative team (Physicians, pharmacist, geneticist and lab manager) that join for planning the most appropriated personalized therapy for their patient.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Agents; Cardiovascular Diseases; Case-Control Studies; Cytochrome P-450 Enzyme System; Genotype; Hospitalization; Humans; Italy; Neoplasms; Pilot Projects

Topics: Acetic Acid; Antineoplastic Agents; Cardiovascular Agents; Heart Diseases; Humans; Neoplasms; Oxalates

Left ventricular (LV) dysfunction due to anthracycline-induced cardiotoxicity (AIC) has been believed to be irreversible. However, this has not been confirmed and standard medical treatment for heart failure (HF) including renin-angiotensin inhibitors and β-blockers may lead to its recovery.. We thus retrospectively studied 350 cancer patients receiving anthracycline-based chemotherapy from 2001 to 2015 in our institution. Fifty-two patients (14.9%) developed AIC with a decrease in LV ejection fraction (LVEF) of 24.1% at a median time of 6 months [interquartile range (IQR) 4-22 months] after anthracycline therapy. By multivariate analysis, AIC was independently associated with cardiac comorbidities including ischemic heart disease, valvular heart disease, arrhythmia, and cardiomyopathy [odds ratio (OR) 6.00; 95% confidence interval (CI) 2.27-15.84, P = 0.00044), lower baseline LVEF (OR per 1% 1.09; 95% CI 1.04-1.14, P = 0.00034). During the median follow-up of 3.2 years, LV systolic dysfunction recovered among 33 patients (67.3%) with a median time of 4 months (IQR 2-6 months), which was independently associated with the introduction of standard medical treatment for HF (OR 9.39; 95% CI 2.27-52.9, P = 0.0014) by multivariate analysis.. Early initiation of standard medical treatment for HF may lead to LV functional recovery in AIC.

Topics: Adult; Aged; Anthracyclines; Antibiotics, Antineoplastic; Cardiotoxicity; Cardiovascular Agents; Female; Heart Failure; Humans; Male; Middle Aged; Neoplasms; Recovery of Function; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

There is a paucity of information about treatment and mortality trends after acute myocardial infarction (AMI) for cancer survivors (CS).. In this population-based study, the authors compared temporal trends of treatments and outcomes (mortality, nonfatal cardiovascular outcomes), among CS and patients without cancer (the noncancer patient [NCP] group) with AMI in Ontario (Canada) using inverse probability treatment weight (IPTW)-adjusted modeling.. Among CS and NCP with AMI in Ontario, similar improvements in mortality and receipt of treatments were observed between 1995 and 2013. However, compared with NCP, CS had a higher risk of mortality and heart failure. Cancer 2018;124:1269-78. © 2017 American Cancer Society.

Topics: Acute Disease; Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cancer Survivors; Cardiovascular Agents; Case-Control Studies; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Myocardial Infarction; Neoplasms; Survival Rate; Time Factors; Treatment Outcome

Liver X receptor (LXR), a member of the nuclear receptor superfamily, mainly serves as a reverse cholesterol transporter in lipid metabolism. It has been demonstrated that LXR is a promising target for the treatment of cardiovascular diseases. LXR is also involved in cancer metabolism, glucose homeostasis, immunity, and various physiological processes. The antitumor function of LXR has become of great interest to researchers in recent years. However, while it is believed that activating LXR with small molecules could be a promising approach to cancer treatment, effective drugs that target LXR are yet to be reported. To find compounds that are potentially capable of activating LXR, we utilized a high-throughput screening method to search the MolMall database for suitable compounds. Seven candidates with lower GB/SA Hawkins scores than the reference ligand T0901317 were identified. Based on the results of molecular dynamics (MD) simulations, binding free energy analysis, and an analysis of the agonism mechanism, ZINC90512020 and ZINC3845032 were predicted to have high affinities for LXR and high relative stabilization, and were therefore selected as potential LXR agonists. Both of these compounds will undergo further development with a view to utilizing them for the treatment of LXR-related cardiovascular diseases or cancers.

Topics: Antineoplastic Agents; Cardiovascular Agents; Cardiovascular Diseases; Computer Simulation; Humans; Ligands; Liver X Receptors; Molecular Docking Simulation; Neoplasms; Protein Binding

Few studies have suggested that patients with myocardial infarction (MI) may be at increased risk of cancer, but further large register-based studies are needed to evaluate this subject. The aim of this study was to assess the incident rates of cancer and death by history of MI, and whether an MI is independently associated with cancer in a large cohort study.. All Danish residents aged 30-99 in 1996 without prior cancer or MI were included and were followed until 2012. Patients were grouped according to incident MI during follow-up. Incidence rates (IR) of cancer and death in individuals with and without MI and incidence rate ratios (IRR, using multivariable Poisson regression analyses) of cancer associated with an MI were calculated.. Of 2,871,168 individuals, 122,275 developed an MI during follow-up, 11,375 subsequently developed cancer (9.3%, IR 19.1/1000 person-years) and 65,225 died (53.3%, IR 106.0/1000 person-years). In the reference population, 372,397 developed cancer (13.0%, IR 9.3/1000 person-years) and 753,767 died (26.3%, IR 18.2/1000 person-years). Compared to the reference population, higher IRs of cancer and death were observed in all age groups (30-54, 55-69 and 70-99 years) and time since an MI (0-1, 1-5 and 5-17 years) in the MI population. MI was associated with an increased risk of overall cancer (IRR 1.14, 95% CI 1.10-1.19) after adjusting for age, sex and calendar year, also when additionally adjusting for chronic obstructive pulmonary disease, hypertension, dyslipidemia, diabetes and socioeconomic status (IRR 1.08, 95% CI 1.03-1.13), but not after further adjustment for the first 6 months post-MI (IRR 1.00, 95% CI 0.96-1.05).. Patients after an MI have increased incidence of cancer, which may be explained by mutual risk, occult cancers and increased surveillance. Focus on risk factor management to reduce cancer and MI is warranted.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Comorbidity; Denmark; Female; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Neoplasms; Prognosis; Registries; Risk Assessment; Risk Factors; Time Factors

Patients developing cancer treatment-related left ventricular dysfunction (CTrLVD) require a prompt therapy. Hypotension, dizziness, and fatigue often limit the use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and β-blockers (BB) in cancer patients who may already be afflicted by these symptoms. Ivabradine is a heart rate-lowering drug that does not cause hypotension and may be used in heart failure with reduced left ventricular ejection fraction (LVEF).. The aim of this paper was to investigate the role of ivabradine to treat CTrLVD.. A retrospective analysis in a cohort of 30 patients with CTrLVD (LVEF < 50%) receiving ivabradine on top of the maximal tolerated dose of ACEi/ARB and BB was performed. We evaluated cardiovascular treatment, oncologic treatment, LVEF, functional class (New York Heart Association [NYHA]), and fatigue during the study period.. Ivabradine was initially started at the dose of 2.5 mg/b.i.d. in most patients and then carefully titrated. Hypotension (70%) and fatigue (77%) were the main causes limiting the treatment with ACEi/ARB and BB. After a mean follow-up of 6.5 months, LVEF increased from 45.1% (SD = 6.4) to 53.2% (SD = 3.9; p < 0.001). When patients were analyzed according to the type of cancer therapy, no difference in LVEF changes across the groups was found. NYHA class ameliorated in 11 patients, while fatigue improved in 8 patients. No serious cardiovascular side effects were reported.. The ability to improve symptoms and LVEF in unfit cancer patients makes ivabradine a reasonable pharmacological tool for treating CTrLVD.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Cardiovascular Agents; Dose-Response Relationship, Drug; Fatigue; Female; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Neoplasms; Retrospective Studies; Trastuzumab; Ventricular Dysfunction, Left

Topics: Antineoplastic Agents; Cardiovascular Agents; Cardiovascular Diseases; Drug Costs; Drug Development; Health Care Costs; Humans; Neoplasms

Episodic breathlessness is a relevant aspect in patients with advanced cancer.. The aim of this study was to assess the different aspects of this clinical phenomenon.. A consecutive sample of patients with advanced cancer admitted to different settings for a period of six months was surveyed. The presence of background breathlessness and episodic breathlessness, their intensity (numerical scale 0-10), and drugs used for treatment were collected. Factors inducing episodic breathlessness and its influence on daily activities were investigated.. Of 921 patients, 29.3% (n = 269) had breathlessness and 134 patients (49.8%) were receiving drugs for background breathlessness. In the multivariate analysis, the risk of breathlessness increased with chronic obstructive pulmonary disease, although it decreased in patients receiving disease-oriented therapy and patients with gastrointestinal tumors. The prevalence of episodic breathlessness was 70.9% (n = 188), and its mean intensity was 7.1 (SD 1.6). The mean duration of untreated episodic breathlessness was 19.9 minutes (SD 35.3); 41% of these patients were receiving drugs for episodic breathlessness. The majority of episodic breathlessness events (88.2%) were triggered by activity. In the multivariate analysis, higher Karnofsky Performance Status levels were significantly related to episodic breathlessness, although patients receiving disease-oriented therapy were less likely to have episodic breathlessness.. This study showed that episodic breathlessness frequently occurs in patients with breathlessness in the advanced stage of disease, has a severe intensity, and is characterized by rapid onset and short duration, which require rapid measures.

Topics: Activities of Daily Living; Aged; Cardiovascular Agents; Comorbidity; Dyspnea; Female; Humans; Karnofsky Performance Status; Male; Middle Aged; Multivariate Analysis; Neoplasms; Palliative Care; Prevalence; Pulmonary Disease, Chronic Obstructive; Time Factors

Breathlessness is common in patients with advanced cancer. Using a multidisciplinary approach for relieving this challenging symptom was believed to be just a theory. The "SOB Program" was implemented in our institution in March 2013.. An audit of medical records before and after implementation of the "SOB Program" was performed to identify any changes in practice after implementation, specifically in the use of nonpharmacologic interventions.. The "SOB Program" is a multidisciplinary service in our department, using both pharmacologic and nonpharmacologic interventions for all patients with advanced cancer who have dyspnea.. There was a marked increase in the use of nonpharmacologic interventions after the "SOB Program" (26.86% preimplementation vs. 89.35% postimplementation). Patients joining the program also had satisfactory improvement in breathlessness.. A multidisciplinary approach for breathlessness control is both feasible and practical. Similar services can be promoted in other palliative care centers.

Topics: Cardiovascular Agents; Dyspnea; Feasibility Studies; Follow-Up Studies; Hong Kong; Humans; Neoplasms; Palliative Care; Retrospective Studies

Topics: Age Factors; Aging; Anticarcinogenic Agents; Aspirin; Cardiovascular Agents; Cardiovascular Diseases; Health Status; Humans; Neoplasms; Primary Prevention; Risk Factors

Dietary intervention studies suggest that flavan-3-ol intake can improve vascular function and reduce the risk of cardiovascular diseases (CVD). However, results from prospective studies failed to show a consistent beneficial effect. Associations between flavan-3-ol intake and CVD risk in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) were investigated. Data were available from 24,885 (11,252 men; 13,633 women) participants, recruited between 1993 and 1997 into the EPIC-Norfolk study. Flavan-3-ol intake was assessed using 7-day food diaries and the FLAVIOLA Flavanol Food Composition database. Missing data for plasma cholesterol and vitamin C were imputed using multiple imputation. Associations between flavan-3-ol intake and blood pressure at baseline were determined using linear regression models. Associations with CVD risk were estimated using Cox regression analyses. Median intake of total flavan-3-ols was 1034mg/d (range: 0-8531mg/d) for men and 970mg/d (0-6695mg/d) for women, median intake of flavan-3-ol monomers was 233mg/d (0-3248mg/d) for men and 217 (0-2712mg/d) for women. There were no consistent associations between flavan-3-ol monomer intake and baseline systolic and diastolic blood pressure (BP). After 286,147 person-years of follow-up, there were 8463 cardiovascular events and 1987 CVD related deaths; no consistent association between flavan-3-ol intake and CVD risk (HR 0.93, 95% CI: 0.87; 1.00; Q1 vs Q5) or mortality was observed (HR 0.93, 95% CI: 0.84; 1.04). Flavan-3-ol intake in EPIC-Norfolk is not sufficient to achieve a statistically significant reduction in CVD risk.

Topics: Adult; Aged; Cardiovascular Agents; Cardiovascular Diseases; Diet; Female; Flavonoids; Humans; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Prospective Studies; Risk Factors

For multiple chemotherapeutics, cardiotoxicity is dose limiting and can lead to substantial morbidity and mortality. Early cardiac intervention has the potential to positively affect clinical course.. We reviewed 247 consecutive patients referred to the Stanford cardiology clinic for cancer therapy-associated cardiac abnormalities from 2004 to 2012. A comprehensive review of records was performed, with documentation of baseline characteristics, cardiac imaging, medications, and clinical course. Seventy-nine patients who had left ventricular ejection fraction (LVEF) declines temporally associated with cancer therapy were included. The most common malignancies were breast (46%) and hematologic (35%); 71% of the patients were female, and overall mean age was 52 years. The primary cancer therapeutics associated with LVEF decline included anthracyclines, trastuzumab, and tyrosine kinase inhibitors. The mean LVEF was 60% before cancer therapy and 40% after cancer therapy. The most common cardiac interventions included beta-blockers (84%) and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (83%). Mean LVEF after cardiac intervention rose to 53%; 77% of patients had LVEF recovery to ≥50%, and 68% of these patients had recovery within 6 months of starting cardiac therapy; 76% of patients were able to continue their planned cancer therapy.. With appropriate cardiac intervention, the majority of patients with LVEF decline from cancer therapy can achieve LVEF recovery and complete their cancer therapy.

Topics: Adult; Aged; Antineoplastic Agents; Cardiovascular Agents; Cohort Studies; Early Medical Intervention; Female; Humans; Male; Middle Aged; Neoplasms; Prognosis; Retrospective Studies; Ventricular Dysfunction, Left

Topics: Antineoplastic Agents; Cardiovascular Agents; Early Medical Intervention; Female; Humans; Male; Neoplasms; Ventricular Dysfunction, Left

Topics: Antineoplastic Agents; Cardiovascular Agents; Early Medical Intervention; Female; Humans; Male; Neoplasms; Ventricular Dysfunction, Left

Topics: Antineoplastic Agents; Cardiovascular Agents; Early Medical Intervention; Female; Humans; Male; Neoplasms; Ventricular Dysfunction, Left

Topics: Cardiovascular Agents; Cardiovascular Diseases; Humans; Life Expectancy; Neoplasms

Multimorbidity, defined as the presence of two or more chronic conditions, leads to a substantial public health burden. This study evaluated its association with adherence with cardiovascular medications in a Chinese population. A proportional stratified sampling was adopted to draw a representative sample of residents living in Henan Province, China. Interviewer-administered surveys were conducted by trained researchers. The outcomes included the number of chronic medical conditions, adherence with long-term medications (MMAS-8), and depressive symptoms (CESD-20). Binary logistic regression analysis was conducted to evaluate if medication adherence was associated with the presence of multimorbidity. From a total of 3866 completed surveys, the proportion of subjects having 0, 1 and ≥2 chronic conditions was 62.6%, 23.8% and 13.5%, respectively. Among 27.6% who were taking chronic medications, 66.6% had poor medication adherence (MMAS-8 score≤6). From binary logistic regression analysis, subjects with poor medication adherence were significantly associated with multimorbidity (adjusted odds ratio [AOR]: 1.35, 95% C.I. 1.02-1.78, p=0.037). Other associated factors included older age (AOR=1.04, 95% C.I. 1.03-1.05, p<0.001), smoking (AOR=1.63, 95% C.I. 1.16-2.30, p=0.005), family history of hypertension (AOR=1.51, 95% C.I. 1.19-1.93, p=0.001), and fair to poor self-perceived health status (AOR=2.15, 95% C.I. 1.69-2.74, p<0.001). Using medication adherence as the outcome variable, multimorbidity was significantly associated with poor drug adherence (AOR=1.34, 95% C.I. 1.02-1.77, p=0.037). Multimorbidity was associated with poorer medication adherence. This implies the need for closer monitoring of the medication taking behavior among those with multiple chronic conditions.

Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Data Collection; Depression; Female; Humans; Male; Medication Adherence; Middle Aged; Neoplasms; Population Surveillance; Young Adult

Research suggests that the quality of non-cancer-related care among cancer survivors (CS) is suboptimal. Secondary disease prevention is an important component of survivorship care that has not been previously evaluated. Our aims were (1) to assess the utilization of and adherence to medications and treatments for the secondary prevention of myocardial infarction (MI) in CS versus non-cancer patients (NCP) and (2) to compare temporal trends in cardiovascular care between these two patient cohorts. Linking data from Medicare, pharmacy assistance programs, and cancer registries, we calculated the percentage of individuals receiving preventive medications (statins, β-blockers, angiotensin-converting enzyme inhibitors) and revascularization interventions (angioplasty, stent, bypass surgery) within 90 days after acute MI in CS and propensity score-matched NCP. We assessed trends over time and determined predictors of appropriate preventive care using modified Poisson regression. We identified 1,119 CS and 7,886 NCP. Compared to NCP, more survivors received statins (38 vs. 31 %) and β-blockers (67 vs. 59 %), but fewer underwent bypass surgery (1.5 vs. 2.8 %) after MI. From 1997 to 2004, both survivors and NCP were increasingly prescribed medications to prevent future coronary events. Over the same time period, receipt of bypass surgery was significantly lower among survivors. Co-morbidities, such as depression and lung disease, and demographic factors, such as advanced age and female, were associated with underuse of preventive care among survivors when compared to NCP. Use of preventive medications and procedures has generally improved, but uptake of bypass surgery among CS still lags behind NCP.

Topics: Aged; Aged, 80 and over; Cardiac Surgical Procedures; Cardiovascular Agents; Cardiovascular Diseases; Female; Humans; Male; Medication Adherence; Neoplasms; Preventive Health Services; Retrospective Studies; Survivors

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antineoplastic Agents; Cardiovascular Agents; Cardiovascular Diseases; Humans; Neoplasms; Randomized Controlled Trials as Topic

Topics: Antineoplastic Agents; Carcinogens; Cardiovascular Agents; Cardiovascular Diseases; History, 18th Century; Humans; Life Expectancy; Neoplasms; Risk Assessment; Risk Factors; Smallpox; Smoking Cessation

Randomized trials have established the benefit of medical therapy and revascularization in the treatment of acute myocardial infarction (MI). Cancer and cardiovascular disease are the 2 most common diseases worldwide. In clinical practice, cancer patients are frequently afflicted with MI. The benefit of medical and/or revascularization therapy in the cancer population with MI is less well known.. Medical and revascularization therapy reduces mortality in cancer patients with MI.. After approval by the institutional review board, we retrospectively reviewed all patients with a discharge diagnosis of acute MI who were admitted to the University of Texas MD Anderson Cancer Center between December 2000 and October 2006 and evaluated the association between cardiac treatments with survival outcomes.. A total of 456 patients with a discharge diagnosis of acute MI were identified and included in the study, of which 386 had non-ST-segment elevation MI (NSTEMI) and 70 had ST-segment elevation MI (STEMI). Compared with patients with NSTEMI, patients who had STEMI were more often prescribed aspirin (66% vs 43%; P = 0.004), β-blockers (61% vs 46%; P = 0.018), and thrombolytic therapy (9% vs 0.3%; P = 0.0001). In the multivariable analysis, aspirin use was associated with a 23% decreased risk of death (hazard ratio [HR]: 0.77, 95% confidence interval [CI]: 0.60-0.98, P = 0.033) and β-blocker use was associated with a 36% decreased risk of death (HR: 0.64, 95% CI: 0.51-0.81, P = 0.0002). Statins (HR: 0.82, P = 0.18) and catheter-based revascularization (HR: 0.57, P = 0.09) did not have an impact on the risk of death. Compared with patients with limited cancer, advanced cancer patients were twice as likely to die (HR: 2.12, 95 CI: 1.47-3.04, P < 0.0001). Previous chemotherapy (P = 0.005) and chest radiotherapy (P = 0.017) were associated with increased 1-year mortality, whereas hyperlipidemia (P = 0.018) was protective.. In this study of cancer patients with MI, medical therapy with aspirin and β-blockers was associated with improved survival. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Topics: Academic Medical Centers; Acute Coronary Syndrome; Adrenergic beta-Antagonists; Aged; Aspirin; Cardiovascular Agents; Chi-Square Distribution; Female; Humans; Kaplan-Meier Estimate; Male; Multivariate Analysis; Myocardial Revascularization; Neoplasms; Platelet Aggregation Inhibitors; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Texas; Thrombolytic Therapy; Time Factors; Treatment Outcome

Topics: Acute Coronary Syndrome; Cardiovascular Agents; Female; Humans; Male; Myocardial Revascularization; Neoplasms; Thrombolytic Therapy

Anthracyclines play a major role in chemotherapeutic regimens for a variety of pediatric cancers, but produce undesirable dose-related cardiotoxicity. Dexrazoxane reduces early myocardial injury during anthracycline treatment, but data remain insufficient to fully understand its cardioprotective effectiveness in treating pediatric cancers and additional research is necessary to find efficient methods of dexrazoxane administration. Therefore, we retrospectively evaluated the cardioprotective effect of dexrazoxane against anthracyclines in 258 pediatric cancer patients who had received any anthracyclines from January 1997 to May 2005 at a tertiary teaching hospital in Korea. The results of this study suggest that the early use of dexrazoxane protects against the development of cardiotoxicity during anthracycline treatment in pediatric cancer patients. Further studies involving larger pediatric cancer patients are needed to evaluate the cardioprotective effect of dexrazoxane at higher cumulative doses of anthracyclines and on late-onset cardiotoxicity in long-term survivors.

Topics: Adolescent; Age Factors; Anthracyclines; Cardiovascular Agents; Cardiovascular Diseases; Child; Child, Preschool; Female; Heart Function Tests; Hospitals, Teaching; Humans; Infant; Male; Neoplasms; Razoxane; Republic of Korea; Retrospective Studies

In a recent article published in The Lancet, investigators studied the impact of daily aspirin use on subsequent cancer deaths. Utilizing data from more than 25,000 patients enrolled in 8 large trials, which were originally intended to study the impact of daily aspirin use on the incidence of cardiovascular events, the authors found a substantial decrease in risk of fatal solid organ malignancies. In particular, the risk reduction was specific to adenocarcinomas. The findings from this study are highly relevant to the thoracic surgeon, with adenocarcinomas of the lung and esophagus among those tumors demonstrating the most profound risk reduction.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Anticarcinogenic Agents; Aspirin; Cardiovascular Agents; Cardiovascular Diseases; Esophageal Neoplasms; Humans; Incidence; Lung Neoplasms; Neoplasms; Preventive Health Services; Risk Assessment; Risk Factors

Doxorubicin may cause a rare but serious cardiotoxicity. Dexrazoxane is a cardioprotectant drug used to reduce the risk of cardiotoxicity in human patients. In this study, 25 tumour-bearing dogs were treated with concurrent doxorubicin and dexrazoxane. The total number of doses of dexrazoxane given was 54 (range 1-5 doses per dog, median 2 doses). Five dogs received more than 165 mg m(2) cumulative doxorubicin dose before starting dexrazoxane. Haematologic, gastrointestinal and cardiovascular toxicities were considered tolerable. The combination of doxorubicin with dexrazoxane was well tolerated with minimal side-effects in this patient cohort. Future studies are required to evaluate potential cardioprotective effects of dexrazoxane given concurrently with doxorubicin.

Topics: Animals; Cardiovascular Agents; Dog Diseases; Dogs; Doxorubicin; Drug Therapy, Combination; Gastrointestinal Diseases; Heart Diseases; Neoplasms; Razoxane

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Cardiovascular Agents; Computer Simulation; Drug-Related Side Effects and Adverse Reactions; Humans; Hypoglycemic Agents; Kinetics; Models, Statistical; Neoplasms; Pharmacology; Pharmacy; Renal Agents; Research Design; Systems Analysis; Therapeutic Equivalency

Myocardial perfusion imaging can predict outcomes in cardiac patients. However, limited data exist regarding its prediction of cardiovascular outcomes in cancer patients. We sought to determine whether myocardial perfusion imaging predicts long-term cardiovascular outcomes in cancer patients.We performed a retrospective review of 787 consecutive patients at our institution who underwent myocardial perfusion imaging from January 2001 through March 2003. The Cox proportional hazard model was applied, and total cardiac events, cardiac death, and all-cause death were determined for 3 years. We considered P <0.05 to be statistically significant.Patients with abnormal myocardial perfusion imaging results were more likely to be male and older, with heart disease, more vascular risk factors, and lower left ventricular ejection fraction (0.52 +/- 0.14 vs 0.63 +/- 0.11; P <0.001) than patients with normal myocardial perfusion imaging results. Multivariate predictors of total cardiac events included age (P = 0.023), hyperlipidemia (P = 0.0021), pharmacologic myocardial perfusion imaging (P <0.01), left ventricular ejection fraction (P <0.001), and abnormal myocardial perfusion imaging (P = 0.012). Multivariate predictors of cardiac death included age (P = 0.026) and left ventricular ejection fraction (P = 0.0001). Multivariate predictors of all-cause death were age (P = 0.0001), atrial fibrillation (P = 0.0012), and smoking (P <0.001). Overall survival was improved when patients took aspirin (P = 0.0002) and upon each unit increase in left ventricular ejection fraction (P <0.001).Myocardial perfusion imaging in cancer patients can predict 3-year cardiac outcomes. Increasing age, atrial fibrillation, and smoking were associated with worse outcomes, whereas higher left ventricular ejection fraction and the taking of aspirin were protective.

Topics: Age Factors; Aged; Aspirin; Atrial Fibrillation; Cardiovascular Agents; Cardiovascular Diseases; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Perfusion Imaging; Neoplasms; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Smoking; Stroke Volume; Time Factors; Ventricular Function, Left

A clear definition for vascular targeting agents (VTAs) and vascular disrupting agents (VDAs) has separated the two as distinct methods of cancer treatment. VDAs differ from VTAs (antiangiogenesis drugs) in their mechanism of action. VTAs attempt to keep new blood vessels from forming and do not act on blood vessels that already feed existing tumors. In contrast, VDAs cause the vascular structure inside a solid tumor to collapse, depriving the tumor of blood and oxygen it needs to survive. Therefore, VDAs are an attractive way to approach the cancer problem by combating developed tumors. The following review discusses six small molecule VDAs, namely DMXAA, ZD6126, TZT1027, CA4P, AVE8062, and Oxi4503, their synthesis, biological mechanism of action, and current clinical status.

Topics: Animals; Antineoplastic Agents; Blood Vessels; Cardiovascular Agents; Flavonoids; Humans; Neoplasms; Terminology as Topic; Tubulin

Older oncology patients with multiple comorbidities are at risk for adverse drug events associated with polypharmacy and drug-drug interactions due to patients' altered pharmacokinetic/pharmacodynamic status and the narrow therapeutic windows associated with anti-neoplastic agents. This study addresses the issue of polypharmacy and potential drug-drug interactions in outpatients in a community setting in the USA, and the prescribing behaviour of oncologists after being made aware of potential drug-drug interactions.. We performed a retrospective cohort study in patients with multiple comorbidities exposed to chemotherapy to profile the potential for adverse drug reactions and to define physicians' responses to risks arising from drug interactions. The medical records of 100 patients aged >or=70 years receiving chemotherapeutic agents at a community-based, university-affiliated medical practice were randomly selected and reviewed. Drug class usage was quantified, and potential drug-drug interactions were assessed and categorized. Treating oncologists were encouraged to modify their prescriptions on the basis of potential interactive drug evaluation reports. Physicians' responses were catalogued.. The mean age of the study population was 78 years (range, 70-90 years). Patients had an average of three comorbid conditions. Each patient received an average of 9 x 1 medications. Cardiovascular drugs were the most common medications that patients used to treat chronic conditions. Carboplatin and paclitaxel were the most frequently used chemotherapeutic agents. Inspite of the potential for drug-drug interactions, physicians made no adjustments to prescriptions.. Given that polypharmacy and the chronic use of multiple drugs are a reality for older patients with cancer and polymorbidities, outcome data need to be generated and motivations/incentives provided for physicians to optimize safe and effective supportive oncologic therapeutics.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Bronchodilator Agents; Cardiovascular Agents; Cardiovascular Diseases; Cohort Studies; Comorbidity; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Gastrointestinal Diseases; Health Services for the Aged; Humans; Interdisciplinary Communication; Lung Diseases; Male; Medical Records; Neoplasms; Nonprescription Drugs; Polypharmacy; Retrospective Studies; Surveys and Questionnaires; United States

Several preclinical studies suggested a role for 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) in the treatment of cancer. The objective of this study was to compare the risk of incident cancer between users of statins and users of other cardiovascular medication.. Data were used from the PHARMO database, containing drug dispensing records from community pharmacies and linked hospital discharge records for residents of eight Dutch cities. The study base included all patients with one or more prescriptions for cardiovascular drugs in the period between January 1, 1985 and December 31, 1998. Cases were identified as patients in the study base with a diagnosis of incident cancer and matched with four to six controls on sex, year of birth, geographic region, duration of follow-up, and index date. The analysis was adjusted for diabetes mellitus; prior hospitalizations; comorbidity; and use of diuretics, angiotensin-converting enzyme inhibitors, calcium-channel blockers, nonsteroidal anti-inflammatory drugs, sex hormones, and other lipid-lowering drug therapies.. In the study base, 3129 patients were identified and matched to 16976 controls. Statin use was associated with a risk reduction of cancer of 20% (adjusted odds ratio [OR], 0.80; 95% CI, 0.66 to 0.96). Our data suggest that statins are protective when used longer than 4 years (adjusted OR, 0.64; 95% CI, 0.44 to 0.93) or when more than 1350 defined daily doses are taken (adjusted OR, 0.60; 95% CI, 0.40 to 0.91).. This observational study suggests that statins may have a protective effect against cancer.

Topics: Aged; Cardiovascular Agents; Case-Control Studies; Enzyme Inhibitors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Neoplasms; Risk; Time Factors

Deoxyribozymes (DNAzymes) comprise an exciting class of nucleic acid molecules that are capable of specific cleavage of target mRNA. Recent reports attest to the potential of this class of molecules in cell culture and preclinical studies, where DNAzymes exhibit the ability to silence disease-associated genes (mainly those associated with cardiovascular disease and cancer). Rigorous testing in preclinical studies is now required before this relatively new entity enters Phase I clinical trials.

Topics: Animals; Antineoplastic Agents; Cardiovascular Agents; Cardiovascular Diseases; DNA, Catalytic; Drug Design; Drug Evaluation, Preclinical; Humans; Neoplasms; RNA, Messenger

Topics: Adolescent; Adult; Age Factors; Aged; Animals; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Lewis Lung; Cardiotonic Agents; Cardiovascular Agents; Chelating Agents; Child; Clinical Trials as Topic; Doxorubicin; Echocardiography; Electrocardiography; Female; Heart; Heart Diseases; Humans; Immunosuppressive Agents; Leukemia, Experimental; Male; Mice; Mice, Inbred C57BL; Neoplasms; Neoplasms, Experimental; Razoxane; Time Factors

1) Should dexrazoxane be used routinely in patients with advanced or metastatic cancer who are at risk of developing cardio toxicity when receiving chemotherapy containing doxorubicin or epirubicin? 2) Do the available data support the use of dexrazoxane when anthracyclines are being used in the adjuvant setting for patients at risk of developing cardiotoxicity?. To make recommendations regarding the use of dexrazoxane to prevent cardiotoxicity in patients with nonhematological malignancies who are receiving anthracycline- containing chemotherapy.. Clinical and subclinical cardiotoxicity, noncardiac toxicity and impact on efficacy outcomes such as response and overall survival are considered.. Evidence was selected, reviewed and synthesized by 2 members of Cancer Care Ontario's Systemic Treatment Disease Site Group (STDSG), formerly the Systemic Treatment Program Committee. Drafts of this document have been circulated and reviewed by members of the STDSG. The STDSG comprises medical oncologists, pharmacists, supportive care personnel and administrators. Community representatives did not participate in the development of this guideline, but they will be included in future guidelines.. Seven randomized controlled trials (RCTs), 2 with placebo control, were available for analysis.. Data for clinical cardiotoxicity from 6 trials were pooled (n = 1070). The meta-analysis indicated that the risk of experiencing clinical cardiotoxicity was significantly reduced by dexrazoxane (risk ratio 0.24; 95% confidence interval [CI] 0.11 to 0.52; p = 0.00031). There was no significant benefit shown in individual trials for objective response or survival.. One of the RCTs revealed a significantly lower objective response rate in the dexrazoxane arm. However, a meta-analysis of objective response across 5 trials of breast cancer patients (n = 818) did not confirm this effect (odds ratio 0.85; 95% CI 0.61 to 1.18; p = 0.33). The use of dexrazoxane increased the incidence of myelosuppression and other noncardiac toxicities, but these were generally mild.. The evidence supports the use of dexrazoxane to provide protection against the cardiotoxicity associated with conventional-dose doxorubicin in patients with advanced but anthracycline-sensitive cancer, in whom the continued use of anthracycline-containing chemotherapy is indicated in the opinion of the treating physician and who have received 300 mg/m2 or more of doxorubicin. The evidence supports the use dexrazoxane to provide protection against the cardiotoxicity associated with conventional-dose epirubicin in patients with advanced but anthracycline-sensitive cancer, in whom the continued use of anthracycline-containing chemotherapy is indicated in the opinion of the treating physicians. There are no data indicating the optimal cumulative dose of epirubicin at which dexrazoxane should be instituted. For doxorubicin, use of dexrazoxane is recommended after the cumulative dose reaches 300 mg/m2 (i.e., 55% of the recommended maximum). A similar formula could be used for epirubicin, that is, institution of dexrazoxane when the cumulative dose of epirubicin reaches 550 mg/m2, as the recommended maximum cumulative dose in Canada is 1000 mg/m2. Preclinical studies did not show any cardioprotectant effect for dexrazoxane when used with mitoxantrone, and no clinical studies have been done. Therefore, dexrazoxane is not recommended for use with mitoxantrone. There is no evidence for or against the use of dexrazoxane in the adjuvant setting for any tumour type. Because of concerns that dexrazoxane may reduce the efficacy of anthracyclines, and because data are not yet available on long-term toxicities, further studies should be performed before the drug is used in this setting.

Topics: Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Breast Neoplasms; Cardiovascular Agents; Clinical Trials as Topic; Doxorubicin; Drug Administration Schedule; Epirubicin; Evidence-Based Medicine; Female; Heart; Heart Failure; Humans; Neoplasms; Odds Ratio; Randomized Controlled Trials as Topic; Razoxane; Time Factors; Treatment Outcome

Because toxicities associated with chemotherapy and radiotherapy can adversely affect short- and long-term patient quality of life, can limit the dose and duration of treatment, and may be life-threatening, specific agents designed to ameliorate or eliminate certain chemotherapy and radiotherapy toxicities have been developed. Variability in interpretation of the available data pertaining to the efficacy of the three United States Food and Drug Administration-approved agents that have potential chemotherapy- and radiotherapy-protectant activity-dexrazoxane, mesna, and amifostine-and questions about the role of these protectant agents in cancer care led to concern about the appropriate use of these agents. The American Society of Clinical Oncology sought to establish evidence-based, clinical practice guidelines for the use of dexrazoxane, mesna, and amifostine in patients who are not enrolled on clinical treatment trials.. A multidisciplinary Expert Panel reviewed the clinical data regarding the activity of dexrazoxane, mesna, and amifostine. A computerized literature search was performed using MEDLINE. In addition to reports collected by individual Panel members, all articles published in the English-speaking literature from June 1997 through December 1998 were collected for review by the Panel chairpersons, and appropriate articles were distributed to the entire Panel for review. Guidelines for use, levels of evidence, and grades of recommendation were reviewed and approved by the Panel. Outcomes considered in evaluating the benefit of a chemotherapy- or radiotherapy-protectant agent included amelioration of short- and long-term chemotherapy- or radiotherapy-related toxicities, risk of tumor protection by the agent, toxicity of the protectant agent itself, quality of life, and economic impact. To the extent that these data were available, the Panel placed the greatest value on lesser toxicity that did not carry a concomitant risk of tumor protection.. Mesna: (1) Mesna, dosed as detailed in these guidelines, is recommended to decrease the incidence of standard-dose ifosfamide-associated urothelial toxicity. (2) There is insufficient evidence on which to base a guideline for the use of mesna to prevent urothelial toxicity with ifosfamide doses that exceed 2.5 g/m(2)/d. (3) Either mesna or forced saline diuresis is recommended to decrease the incidence of urothelial toxicity associated with high-dose cyclophosphamide use in the stem-cell transplantation setting. Dexrazoxane: (1) The use of dexrazoxane is not routinely recommended for patients with metastatic breast cancer who receive initial doxorubicin-based chemotherapy. (2) The use of dexrazoxane may be considered for patients with metastatic breast cancer who have received a cumulative dosage of 300 mg/m(2) or greater of doxorubicin in the metastatic setting and who may benefit from continued doxorubicin-containing therapy. (3) The use of dexrazoxane in the adjuvant setting is not recommended outside of a clinical trial. (4) The use of dexrazoxane can be considered in adult patients who have received more than 300 mg/m(2) of doxorubicin-based therapy for tumors other than breast cancer, although caution should be used in settings in which doxorubicin-based therapy has been shown to improve survival because of concerns of tumor protection by dexrazoxane. (5) There is insufficient evidence to make a guideline for the use of dexrazoxane in the treatment of pediatric malignancies, with epirubicin-based regimens, or with high-dose anthracycline-containing regimens. Similarly, there is insufficient evidence on which to base a guideline for the use of dexrazoxane in patients with cardiac risk factors or underlying cardiac disease. (6) Patients receiving dexrazoxane should continue to be monitored for cardiac toxicity. Amifostine: (1) Amifostine may be considered for the reduction of nephrotoxicity in patients receiving cisplatin-based chemoth

Topics: Adult; Amifostine; Antineoplastic Agents; Cardiovascular Agents; Humans; Mesna; Neoplasms; Protective Agents; Radiation-Protective Agents; Radiotherapy; Razoxane

Topics: Adult; Antibiotics, Antineoplastic; Antineoplastic Agents; Cardiovascular Agents; Child; Heart; Heart Diseases; Humans; Neoplasms; Razoxane

Topics: Adult; Animals; Antibiotics, Antineoplastic; Cardiovascular Agents; Child; Heart; Heart Diseases; Humans; Neoplasms; Razoxane

Topics: Antineoplastic Agents; Antioxidants; beta Carotene; Cardiovascular Agents; Cardiovascular Diseases; Carotenoids; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Neoplasms; Vitamin E

The susceptibility of a tissue to the toxic and/or carcinogenic effects of chemicals is determined by a variety of factors, which include their rate of metabolic activation by the cytochrome P450-dependent monooxygenases. Individual differences in the levels of cytochrome P450 expression would be expected, and are known, to give rise to profound differences in toxicological response. Such effects are almost best exemplified by the sex differences observed in the toxic effects of a variety of nephrotoxins and carcinogens. In recent work, we have shown that in species such as the mouse and rat almost all cytochrome P450 enzymes in the kidney are sexually differentiated. This difference in cytochrome P450 regulation is mediated by testosterone and explains the large differences observed in the metabolic activation, toxicity and carcinogenicity of chloroform and possibly of other compounds such as ochratoxin A. In addition to hormonal or environmental influences on cytochrome P450 expression, genetic factors have also been shown to be important. In man, this is best exemplified by the genetic polymorphism observed in the metabolism of debrisoquine and approximately 25 other drugs. This genetic defect affects approximately 5-10% of the Caucasian population and has been associated with altered susceptibility to cancer. In this presentation, the development of a simple DNA-based assay to identify affected individuals is described. Use of this assay will allow clarification of the reported association of this genetic polymorphism to susceptibility to Balkan nephropathy and cancer.

Topics: Animals; Balkan Nephropathy; Base Sequence; Biotransformation; Carcinogens; Cardiovascular Agents; Cytochrome P-450 CYP2D6; Cytochrome P-450 Enzyme System; Disease Susceptibility; DNA; DNA Mutational Analysis; Dogs; Enzyme Induction; Female; Genes; Genetic Predisposition to Disease; Humans; Inactivation, Metabolic; Incidence; Isoenzymes; Kidney; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Mixed Function Oxygenases; Molecular Sequence Data; Neoplasms; Phenotype; Polymorphism, Genetic; Psychotropic Drugs; Rabbits; Rats; Sex Factors

Topics: Adrenal Cortex Hormones; Cardiovascular Agents; Glucocorticoids; Lymph Nodes; Lymphatic Metastasis; Neoplasms; Neoplasms, Experimental; Pharmacology; Rats; Research

Topics: Antihypertensive Agents; Cardiovascular Agents; Ergot Alkaloids; Humans; Methotrimeprazine; Neoplasms; Serotonin; Serotonin Antagonists

Topics: Adrenal Cortex Hormones; Cardiovascular Agents; Dermatologic Agents; Glucocorticoids; Neoplasms

Topics: Cardiovascular Agents; Humans; Muscle Relaxants, Central; Neoplasms; Nervous System Diseases; Paraneoplastic Polyneuropathy

Topics: Cardiovascular Agents; Cholinesterase Inhibitors; Humans; Muscle Relaxants, Central; Neoplasms; Orbit; Phosphates

Topics: Cardiovascular Agents; Disease; Humans; Male; Muscle Relaxants, Central; Muscle Spasticity; Neoplasms; Parasympatholytics; Prostate; Prostatic Neoplasms; Ureter; Ureteral Diseases; Urinary Tract Infections

Topics: Adrenal Cortex Hormones; Cardiovascular Agents; Humans; Mononuclear Phagocyte System; Neoplasms