Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Targeted therapies, which include monoclonal antibodies and small molecule inhibitors, have significantly changed the treatment of cancer over the past 10 years. These drugs are now a component of therapy for many common malignancies, including breast, colorectal, lung, and pancreatic cancers, as well as lymphoma, leukemia, and multiple myeloma. The mechanisms of action and toxicities of targeted therapies differ from those of traditional cytotoxic chemotherapy. Targeted therapies are generally better tolerated than traditional chemotherapy, but they are associated with several adverse effects, such as acneiform rash, cardiac dysfunction, thrombosis, hypertension, and proteinuria. Small molecule inhibitors are metabolized by cytochrome P450 enzymes and are subject to multiple drug interactions. Targeted therapy has raised new questions about the tailoring of cancer treatment to an individual patient's tumor, the assessment of drug effectiveness and toxicity, and the economics of cancer care. As more persons are diagnosed with cancer and as these patients live longer, primary care physicians will increasingly provide care for patients who have received targeted cancer therapy.
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PMID:Targeted therapies: a new generation of cancer treatments. 1829 54

Among antiangiogenic agents, thalidomide is not the most potent nor the most specific even so when venous thromboembolic events have been reported with the prescription of thalidomide in multiple myeloma. This side effect has been related to the antiangiogenic effect of this immunomodulator. In keeping with this observation venous thromboembolic events have been reported in other indications of thalidomide and with thalidomide analogues (Lenalidomide and Actimid). The thrombotic side effects are mostly venous but arterial thrombotic events are also observed with the use of these molecules. With the other and more specific antiagiogenic agents an increase in thrombotic events are also observed. This increase was not immediately evident since the situation in which they are prescribed (metastatic cancers) are already characterized by a high rate of thrombotic events. The prothrombotic effect of antiangiogenic agents are probably linked to an effect on endothelium (decrease of antithrombotic activities and stimulation of a prothrombotuic state). The other sides effects of antiangiogenic agents (hemorrhages, hypertension, proteinuria, microangiotpahia, delay in scaring) are also probably related to endothelial effects. The prothrombotic effect of antoangiogenic agents appears as potentiating the prothrombotic conditions of the disease (myeloma, cancer) and the prothombotic effects of the associated treatments (chemotherapy, high dose corticosteroids, erythropoietin). The increased thrombotic risk linked to prescription of antiangiogenic agents and specially of thalidomide and analogues for multiple myeloma is such that it is recommended to associate a preventive antithrombotic treatment. Some efficacy has been reported with the use of aspirin, oral anticoagulant or low molecular weight heparin. No head to head comparative trial do not allow to prefer one strategy. From published data full dose oral anticoagulants appear to confer the highest hemorrhagic risk and perhaps low molecular weight heparin the best benefit-risk ratio.
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PMID:[Thromboembolic risk associated with use of angiogenesis inhibitors used for the treatment of cancers]. 1845 Mar 88

We present a case of a 76-year-old Japanese man with hypertension and multiple myeloma (MM) presented with syncope and sinus bradycardia. Thalidomide therapy for MM was added to longstanding atenolol therapy one month prior to presentation. His heart rate (HR) was around 70 beats per minute (bpm) before addition of Thalidomide. His HR on presentation was less than 30 bpm. He was treated with intravenous atropine followed by temporary pacemaker and taken off atenolol. His HR returned to around 70 bpm few days after discontinuation of atenolol, even though he was still taking thalidomide, permitting outpatient management without a pacemaker. Both thalidomide and atenolol have been reported to cause bradycardia. Neither agent caused bradycardia when used alone in this patient, but simultaneous use caused symptomatic bradycardia. As thalidomide is prescribed more frequently, clinicians should be aware of the possibility of drug-induced sinus bradycardia due to the interaction of thalidomide and beta-blockers.
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PMID:Syncope and sinus bradycardia from combined use of thalidomide and beta-blocker. 1861 49

The purpose of this study is to investigate the efficacy and safety of recombinant erythropoietin-beta in the treatment of anemic patients with multiple myeloma (MM), low-grade non-Hodgkin's lymphoma (NHL), and chronic lymphocytic leukemia (CLL). From December 2005 to November 2006, the patients with MM, low-grade NHL, and CLL were enrolled in this study, male or female, aged > or = 18 years, transfusion-dependant, and receiving anti-neoplasia chemotherapy. Recombinant human erythropoietin-beta was used in this study with the dose initiated at 150 IU/kg, thrice a week, subcutaneously. The total treatment duration was 12 weeks. The primary endpoint of the study is response rate (RR), which is defined as hemoglobin increasing > or = 2 g/dL comparing to baseline level, or returning to normal range, without any transfusion within 6 weeks of evaluation. Fifty out of 82 (64.6%) patients enrolled in this study responded to the treatment and 29 patients had no response. Hypertension (12.2%) is the most common adverse effect; however, all the adverse events were mild, categorized in NCI grade I or II. We conclude that recombinant erythropoietin-beta was effective in the treatment of anemia of the patients with MM, NHL, and CLL, as well as it is well-tolerated.
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PMID:A multi-center open-labeled study of recombinant erythropoietin-beta in the treatment of anemic patients with multiple myeloma, low-grade non-Hodgkin's lymphoma, or chronic lymphocytic leukemia in Chinese population. 1862 3

Pazopanib, which is being developed by GlaxoSmithKline plc, is an oral, second-generation multi-targeted tyrosine kinase inhibitor that targets VEGFR, platelet-derived growth factor receptor and c-kit, key proteins responsible for tumor growth and survival. Pazopanib exhibited good potency against all of the human VEGFRs and closely related tyrosine receptor kinases in vitro, and demonstrated antitumor activity in several human tumor xenografts, including renal cell carcinoma (RCC), and breast and lung cancer. In phase I and II clinical trials, pazopanib was generally well tolerated with the main side effects being hypertension, fatigue or gastrointestinal disorders. Pazopanib alone caused a decrease in tumor size and stable disease in a significant number of patients, including those with RCC, NSCLC and gynecological tumors. The combination of pazopanib with lapatinib was effective in patients with breast cancer. At the time of publication, pazopanib monotherapy was being evaluated in phase III trials in patients with RCC and as combination therapy with lapatinib in patients with breast cancer. In addition, phase I and II trials were being conducted to assess pazopanib alone or in combination with a range of chemotherapeutics in patients with solid tumors or multiple myeloma.
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PMID:Pazopanib, a VEGF receptor tyrosine kinase inhibitor for cancer therapy. 1903 39

We report a 59-year-old acromegalic woman, who presented with generalized bone pain, weakness, fatigue and foamy urine, who was found to have multiple myeloma (MM); and a 60-year-old acromegalic woman with dizziness, vomiting and abdominal pain, high blood pressure and splenomegaly that was posteriorly diagnosed as having Waldenstrom's macroglobulinemia (WM). Acromegaly is an uncommon disease and epidemiological studies have provided increasingly debated evidence that elevated IGF-I levels might enhance the neoplastic risk, and that cancers constitute the third leading cause of mortality in acromegaly. It is known that GH and IGF-I can activate B cell lymphocytes, and that IGF-I receptor is universally expressed in MM cells. Although the complication of acromegaly with WM or MM in patients has rarely been reported until now, we described two case reports of acromegalic patients with those hematological neoplasias, which allow a discussion about this controversial issue.
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PMID:Hematologic neoplasias and acromegaly. 1933 40

Vandetanib is a novel, orally available inhibitor of different intracellular signaling pathways involved in tumor growth, progression, and angiogenesis: vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and REarranged during Transfection tyrosine kinase activity. Phase I clinical trials have shown that vandetanib is well tolerated as a single agent at daily doses < or =300 mg. In the phase II setting, negative results were observed with vandetanib in small cell lung cancer, metastatic breast cancer, and multiple myeloma. In contrast, three randomized phase II studies showed that vandetanib prolonged the progression-free survival (PFS) time of patients with non-small cell lung cancer (NSCLC) as a single agent when compared with gefitinib or when added to chemotherapy. Rash, diarrhea, hypertension, fatigue, and asymptomatic QTc prolongation were the most common adverse events. Antitumor activity was also observed in medullary thyroid cancer. Four randomized phase III clinical trials in NSCLC are exploring the efficacy of vandetanib in combination with docetaxel, the Zactima in cOmbination with Docetaxel In non-small cell lung Cancer (ZODIAC) trial, or with pemetrexed, the Zactima Efficacy with Alimta in Lung cancer (ZEAL) trial, or as a single agent, the Zactima Efficacy when Studied versus Tarceva (ZEST) and the Zactima Efficacy trial for NSCLC Patients with History of EGFR-TKI chemo-Resistance (ZEPHYR) trials. Based on a press release by the sponsor of these trials, the PFS time was longer with vandetanib in the ZODIAC and ZEAL trials; the ZEST trial was negative for its primary superiority analysis, but was successful according to a preplanned noninferiority analysis of PFS. Ongoing phase II and III clinical trials will better define the appropriate schedule, the optimal setting of evaluation, and the safety of long-term use of vandetanib.
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PMID:Vandetanib (ZD6474), a dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) tyrosine kinases: current status and future directions. 1934 11

Aims. To describe the baseline characteristics of an Australian population-based cohort of rheumatoid arthritis (RA) patients commencing biological therapy. Methods. Descriptive analysis from the Australian Rheumatology Association Database (ARAD). Results. Up to October 2006, there were 681 RA patients taking biologics enrolled in ARAD. Baseline data were available for 624 (72% female, mean (SD) age 57.0 (12.5) years). Of these, 59.5% reported at least one comorbid condition, most commonly hypertension (35.7%) and osteoporosis (30.4%); 61 (9.8%) had a history of malignancy (35 nonmelanoma skin, 5 breast, 4 bowel, 5 cervix, 3 melanoma, 3 prostate and 1 each of lip, lung, myeloma, testis, uterus, vagina). Self-reported infections within the previous 6 months were common (71.5%). Conclusions. History of comorbidities, including recent infections, is common among Australian RA patients commencing biologics, and 10% have a history of malignancy. This may impact future evaluations of health outcomes among this population, including attribution of adverse events of biologic therapy.
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PMID:Baseline comorbidities in a population-based cohort of rheumatoid arthritis patients receiving biological therapy: data from the Australian rheumatology association database. 2013 Aug 3

Background. Monoclonal gammopathy of undetermined significance (MGUS) is rarely complicated by amyloidosis. Case. A 66-year-old white male presented to the emergency room (ER) after an unwitnessed fall and change in mental status. Patient was awake and alert but not oriented. There was no focal deficit on neurological exam. Past medical history (PMH) included hypertension, hypercholesterolemia, aortic valve replacement (nonmetallic), incomplete heart block controlled by a pacemaker and IgG- IgA type Monoclonal Gammopathy of Undetermined Significance. The MGUS was diagnosed 9 months ago on serum protein electrophoresis (SPEP) as patient was referred to the outpatient clinic for hyperglobulinemia on routine blood work. In ER, a head-computed tomography (CT) revealed multiple parenchymal hemorrhagic lesions suspicious for metastases. A CT chest, abdomen and pelvis revealed numerous ground-glass and solid nodules in the lungs. Lower extremity duplex and transesophageal echocardiogram were negative. Serial blood cultures and serologies for cryptococcus and histoplasmosis, antineutrophil cytoplasmic antibody (ANCA), antinuclear antibody (ANA), rheumatoid factor (RF), cryoglobulin, and antiglomerular basement membrane (anti-GBM) antibodies were all negative. CT guided lung biopsy was positive for Thioflavin T amyloid deposits. Brain biopsy was positive for eosinophilic material (similar to the lungs) but negative for Thioflavin T stain. The patient's clinical status continued to deteriorate with cold cyanotic fingers developing on day 12 and a health care acquired pneumonia, respiratory failure, and fungemia on day 18. On day 29, family withdrew life support and denied any autopsies. Conclusion. Described is an atypical course of MGUS complicated by amyloidosis of the lung and nonamyloid eosinophilic deposition in the brain. As MGUS might be complicated by diseases such as amyloidosis and multiple myeloma, a scheduled follow-up of these patients is always necessary. Further research is needed in order to better define the optimal treatment and management strategies of MGUS and its complications.
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PMID:Monoclonal gammopathy of undetermined significance with amyloid deposition in the lung and non-amyloid eosinophilic deposition in the brain: a case report. 2030 May 49

This prospective study evaluated the risk of arterial thrombosis in 195 consecutive patients aged 18 to 65 years with newly diagnosed multiple myeloma (MM). All patients were treated with 3 cycles of VAD (vincristine, doxorubicin, and dexamethasone) or TAD (thalidomide-AD) or PAD (bortezomib-AD) in national trials, followed by high-dose melphalan and autologous stem cell transplantation. For a period of 522 patient-years, 11 of the 195 patients (5.6%) developed arterial thrombosis. The highest incidence was seen during induction chemotherapy courses. Median age at onset of arterial thrombosis was 59 years (range, 43-65 years). Hypertension and smoking were significantly associated with arterial thrombosis with a relative risk of 11.7 (2.23-61.2) and 15.2 (1.78-130), respectively. Factor VIII levels (FVIII:C) correlated significantly with age (P = .02) and higher International Scoring System (ISS) stage (P = .001). A higher FVIII:C was associated with arterial thrombosis (hazard ratio [HR] = 1.85; 95% confidence interval [CI] = 0.99-3.47) after adjustment for age, ISS score, and assigned treatment arm. MM patients have an increased risk for arterial thrombotic events during and after induction chemotherapy. Hypertension, smoking, and high factor VIII levels, possibly reflecting disease activity, contribute to the risk of arterial thrombosis.
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PMID:High incidence of arterial thrombosis in young patients treated for multiple myeloma: results of a prospective cohort study. 2061 23


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