Ali Zalpour

Vascular Endothelial Growth Factor Inhibitor-Induced Hypertension: Basics for Primary Care Providers

Frequently, primary care providers continue to manage the overall medical care of cancer patients. With newer and often more potent antitumor agents, patients may present to their local physicians with drug-induced toxicities such as hypertension induced by vascular endothelial growth factor (VEGF) inhibitors. It is imperative that these healthcare providers are aware of basic aspects of this drug class, as its use has increased significantly in the last several years. Uncontrolled or malignant hypertension due to these agents should be recognized readily and treated early to prevent more severe outcomes. This overview provides a brief background on the role of VEGF and angiogenesis in tumor metabolism as well as theories of the mechanism of VEGF inhibitors and hypertension. Helpful clinical practice aspects including the types of inhibitors used in the United States and their pharmacologic characteristics will be discussed. Also, diagnosis and treatment of hypertension induced by vascular endothelial growth factors are reviewed. A summary of key aspects of this drug class and hypertension is included.

A retrospective study of venous thromboembolism in acute leukemia patients treated at the University of Texas MD Anderson Cancer Center

The purpose was to determine the incidence and prevalence of venous thromboembolism (VTE) in acute leukemia patients from our institution. We conducted a retrospective study on newly diagnosed acute leukemia patients who presented at our institution from November 1999 to May 2005. Descriptive statistics and cross‐tabulation were used to describe patient characteristics. Measures of morbidity were used to address VTE risk. Chi‐square testing, Fishers exact testing, Mann–Whitney analyses, or median testing were used to determine between‐group differences. Data analyses were conducted using Stata version 11 (Stata Corp., College Station, TX). Two hundred and ninety‐nine patients with acute lymphoblastic leukemia (ALL) and 996 patients with acute myeloid leukemia (AML) were included. After excluding patients diagnosed with VTE prior to or at the time of leukemia diagnosis, during the mean time follow‐up period of 2.5 years (range: 0.0025–10.3 years), the overall incidence rate of VTE was 3.7 per 100 person‐years: 4.2 per 100 person‐years for ALL and 3.4 per 100 person‐years for AML. Among all patients, the majority (80.6%) developed VTE within 12 months after diagnosis and during thrombocytopenia. The most common VTE was central venous catheter (CVC)‐associated upper‐extremity deep venous thrombosis. Pulmonary embolism occurred in 15% of ALL patients and 8% of AML patients. VTE recurred in 20.7% of ALL patients and 18.6% of AML patients. VTE occurs frequently in patients with acute leukemia. Studies are needed to identify risk factors for the development and recurrence of VTE among patients with acute leukemia and to establish more effective methods for preventing and treating VTEs in leukemia patients who have thrombocytopenia and/or CVC.

Meta-analysis of cardiovascular toxicity risks in cancer patients on selected targeted agents

PurposeThe purpose was to estimate the risk and severity of cardiovascular toxicities associated with selected targeted agents.MethodsWe searched English-language literature for randomized clinical trials published between January 1, 2000 and November 30, 2013 of targeted cancer therapy drugs approved by the FDA by November 2010. One hundred ten studies were eligible. Using meta-analytic methods, we calculated the relative risks of several cardiovascular toxicities [congestive heart failure (CHF), decreased left ventricular ejection fraction (DLVEF), myocardial infarction (MI), arrhythmia, and hypertension (HTN)], adjusting for sample size using the inverse-variance technique. For each targeted agent and side effect, we calculated the number needed to harm. Results: Regarding CHF, trastuzumab showed significantly greater risk of all-grade and high-grade CHF. There was significant increased risk of all-grade DLVEF with sorafenib, sunitinib, and trastuzumab and high-grade DLVEF with bevacizumab and trastuzumab. Sorafenib was associated with significant increased all-grade risk of MI based on one study. None was associated with high-grade risk of MI or increased risk of arrhythmia. Bevacizumab, sorafenib, and sunitinib had significant increased risk of all-grade and high-grade HTN.ConclusionsSeveral of the targeted agents were significantly associated with increased risk of specific cardiovascular toxicities, CHF, DLVEF, and HTN. Several had significant increased risk for high-grade cardiovascular toxicities (CHF, DLVEF, and HTN). Patients receiving such therapy should be closely monitored for these toxicities and early and aggressive treatment should occur. However, clinical experience has demonstrated that some of these toxicities may be reversible and due to secondary effects.

Update on Edoxaban for the prevention and treatment of thromboembolism: Clinical applications based on current evidence

Vitamin K antagonists (VKA) and heparins have been utilized for the prevention and treatment of thromboembolism (arterial and venous) for decades. Targeting and inhibiting specific coagulation factors have led to new discoveries in the pharmacotherapy of thromboembolism management. These targeted anticoagulants are known as direct oral anticoagulants (DOACs). Two pharmacologically distinct classes of targeted agents are dabigatran etexilate (Direct Thrombin Inhibitor (DTI)) and rivaroxaban, apixaban, and edoxaban (direct oral factor Xa inhibitors (OFXaIs)). Emerging evidence from the clinical trials has shown that DOACs are noninferior to VKA or low-molecular-weight heparins in the prevention and treatment of thromboembolism. This review examines the role of edoxaban, a recently approved OFXaI, in the prevention and treatment of thromboembolism based on the available published literature. The management of edoxaban in the perioperative setting, reversibility in bleeding cases, its role in cancer patients, the relevance of drug-drug interactions, patient satisfaction, financial impacts, and patient education will be discussed.

Role of Factor Xa Inhibitors in Cancer-Associated Thrombosis: Any New Data?

The association between cancer and venous thromboembolism (VTE) has been well documented in the literature. Prevention and treatment of VTE in cancer patients is imperative. Typically, the mainstay regimen for VTE prevention and treatment has been anticoagulation therapy, unless contraindicated. This therapy consists of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), factor Xa inhibitor, or vitamin K antagonist (VKA). Current guidelines recommend LMWH over VKA for the treatment of VTE in cancer patients. Factor-specific anticoagulants have been proven safe and effective, and recently factor Xa inhibitors have emerged as a treatment alternative to heparins and VKA. Currently, three factor Xa inhibitors have been identified: fondaparinux (the only one approved so far by the US Food and Drug Administration), idraparinux (in clinical trials), and idrabiotaparinux (in clinical trials). This paper will examine the role of these agents, focusing on fondaparinux, for the prevention and treatment of VTE in cancer patients.

Clinical utility of apixaban in the prevention and treatment of venous thromboembolism: Current evidence

Anticoagulation with heparin and vitamin K antagonist has been the mainstay of prevention and treatment of venous thromboembolism (VTE) for many years. In recent years, novel oral anticoagulants such as dabigatran etexilate (a direct thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (a direct factor Xa inhibitor) have emerged for the prevention and treatment of VTE. Novel oral anticoagulants have been shown to be noninferior to vitamin K antagonist or heparin in the prevention and treatment of VTE. This review specifically examines the role of apixaban in the prevention and treatment of VTE based on the available literature. The management of apixaban in the perioperative setting is also explored because some patients on apixaban may require surgical intervention. Finally, we discuss the management of apixaban-induced major bleeding complications, the relevance of drug–drug interactions, and patient education.

Predictors of Anticoagulation in Hospice Patients With Lung Cancer

Guidelines recommend lifelong anticoagulation in patients with cancer and a history of thromboembolism, but the use of anticoagulation in hospice has not been described. A retrospective study of medication data was conducted to determine patterns of anticoagulant use and predictors of type of anticoagulant prescribed for hospice patients with lung cancer.

Intercostal Nerve Blocks With Liposomal Bupivacaine: Demonstration of Safety, and Potential Benefits

Liposomal bupivacaine is designed to allow drug diffusion for up to 96 hours following a single administration. Our study aimed to evaluate the safety of liposomal bupivacaine as an intercostal nerve block as part of an enhanced recovery pathway using standardized multimodality pain regimen compared with epidural analgesia in propensity score-matched patients undergoing lung resection. Patients undergoing lung resection (n?=?1737; 2010-2015) were stratified by treatment with intraoperative liposomal bupivacaine intercostal block vs epidural analgesia. We performed 2 propensity score matching analyses. In the first, propensity for treatment with liposomal bupivacaine was estimated using pretreatment variables and the patients were matched on the propensity score. The variables were age, neoadjuvant therapy, extent of resection, and the Zubrod score. In the second, the propensity score matching was performed only in patients who had a thoracotomy. Perioperative outcomes were compared between groups using paired statistical analysis techniques. In the first analysis (n?=?1236), there were more thoracotomies performed in the epidural group (P?<?0.0001). The rate of pulmonary, gastrointestinal, wound, and neurologic complications was similar between the groups, but there were more cardiovascular complications in the epidural arm (P?=?0.02), mostly atrial arrhythmias. In the second analysis (n?=?494), there were no differences in the rate of postoperative complications between the groups. The use of liposomal bupivacaine is not associated with a rise in perioperative complications when compared with epidural analgesia. Liposomal bupivacaine is a safe adjunct to the management of pain of patients undergoing pulmonary surgery.

Meta-analysis: Risk of congestive heart failure (CHF) in selected targeted agents.

64 Background: Congestive heart failure (CHF) is among the most serious cardiovascular side effects of targeted agents (TA) impacting the clinical outcomes (including survival) of cancer patients on this therapy. Although clinical trials have reported this toxicity, often sample sizes are small and systemic evaluations are lacking. The objective of this study is to estimate risk and severity of CHF due to selected TAs. METHODS We identified 110 English language studies of 26 TAs approved by the Food and Drug Administration as of November 2013 via MEDLINE. Of those, 8 studies including nearly 8000 patients provided TA-related data on the incidence and severity of CHF. Using meta-analytic methods, we calculated the relative risks of CHF, adjusting for sample size using the inverse variance technique. For each TA, we also determined the number needed to harm. RESULTS See table. CONCLUSIONS In 5 studies including more than 7,000 patients, trastuzumab showed significantly greater risk of CHF. For every 9 patients treated with trastuzumab, there was 1 additional case of CHF compared to control regimens. A careful patient selection before therapy and early detection of CHF by judicious monitoring of patients on this therapy may prevent serious complications and allow maintenance of cancer treatment. [Table: see text].

Practice patterns and outcomes of rivaroxaban usage in patients with cancer.

194 Background: Patients with cancer have an increased risk of venous thromboembolism (VTE) and frequently require anticoagulation. In addition, many patients with cancer also have comorbidities such as atrial fibrillation (AF) and are on stroke prevention. Rivaroxaban (RV) is an oral (factor Xa inhibitor) used in these scenarios; however, there is little experience utilizing this agent in patients with cancer. Our aim is to describe practice patterns and outcomes of RV usage in patients with cancer. METHODS We conducted a retrospective study of 62 patients with cancer receiving RV for at least 5 days for VTE or non-valvular AF from 1/1/2012 through 10/31/2015. Practice patterns included RV perioperative use and blood and platelet transfusions. Outcomes of interest were recurrent VTE and bleeding. Descriptive statistics were utilized to summarize demographic and clinical variables. RESULTS Of 62 patients with cancer, the mean age was 62 years (range 31-83), 50% were male, and 77% white. The most common cancer types were gastrointestinal 9 (15%), sarcoma 9 (15%), and breast and hematologic each with 8 (13%). Of those, 49 (79%) had VTE, 9 AF (15%), and 4 (7%) had both. 42 (68%) patients were switched to RV from a prior anticoagulant, the majority from low molecular weight heparin. 22 (36%) had RV withheld temporarily; 15 due to surgical procedure and 5 due to bleeding. 5 (33%) received bridging anticoagulation prior to surgery. RV was held a mean of 2 days prior to surgery and resumed 9 days post-op. 14 (21%) received blood and 2 (3%) received platelet transfusions while on RV. 2 (3%) patients had VTE recurrence while on RV. 18 (29%) discontinued RV due to bleeding, 5 (28%) due to hematuria and only 1 patient due to thrombocytopenia (6%). There were no major bleeds or deaths related to RV. CONCLUSIONS RV was used in solid and hematologic cancers. The majority were transitioned from another anticoagulant. Although VTE recurrence was low, discontinuation of RV due to bleeding was higher. Further study of the use of RV in patients with cancer is needed for continued guidance of appropriate and safe usage.