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)

Angiogenesis is essential for tumor growth, invasion and metastasis, and is mediated, at least in part, by a large family of VEGF ligands and receptors. Ramucirumab, which is being developed by ImClone Systems Inc, is a fully human mAb that binds human VEGFR-2, thus blocking VEGF binding and inhibiting angiogenesis. Proof-of-concept preclinical studies with the mouse mAb DC-101 supported this hypothesis, and ramucirumab inhibited cell proliferation in vitro, as well as tumor progression in mouse xenograft models of human cancer. Ramucirumab was well tolerated on weekly and fortnightly schedules in phase I clinical trials in patients with advanced cancers; mechanism-related DLTs were hypertension and deep venous thrombosis. Stable disease was also observed in several patients treated on either schedule, and several patients on the weekly schedule exhibited partial responses. At the time of publication, ramucirumab was undergoing assessment in phase II trials as a monotherapy in hepatocellular, renal cell and ovarian carcinomas. Ramucirumab was also in phase II trials in combination with dacarbazine in melanoma, with mitoxantrone/prednisone in prostate cancer, with carboplatin/paclitaxel in NSCLC and with oxaliplatin/folinic acid/5-fluorouracil in colorectal cancer. A phase III trial in combination with docetaxel in breast cancer was also ongoing. Pending results from these trials, ramucirumab may be a useful addition to current antiangiogenic therapies. The results are awaited with interest.
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PMID:Ramucirumab, a fully human mAb to the transmembrane signaling tyrosine kinase VEGFR-2 for the potential treatment of cancer. 1951 49

Overexpression of vascular endothelial growth factor (VEGF) by tumor cells promotes angiogenesis, which correlates with progressive tumor growth and poor outcomes in many types of cancer. Bevacizumab inhibits VEGF to promote regression of tumor vessels by limiting blood supply and tumor growth, enhancing delivery of chemotherapy, and inhibiting formation of new vessels. Combined with chemotherapy, bevacizumab prolongs progression-free and overall survival over chemotherapy alone in patients with metastatic carcinoma of the colon and rectum; unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC); and metastatic HER2-negative breast cancers (mBC). Side effects, including hypertension, proteinuria, bleeding, arterial thrombotic events, and impaired wound healing, can be clinically significant, particularly in patients with risk factors. To optimize patient outcomes, nurses should understand bevacizumab's role in cancer therapy, recognize symptoms of toxicity, and manage its side effects. This article describes the rationale for bevacizumab in the treatment of metastatic colorectal cancer, NSCLC, and mBC and discusses patient selection, treatment duration, and side-effect management to support the role of oncology nurses in caring for, educating, and enhancing treatment adherence among patients with cancer receiving bevacizumab. Two case studies are presented as examples of the complex scenarios nurses may encounter regarding these issues.
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PMID:Oncology nursing in a new era: optimizing treatment with bevacizumab. 1979 13

Angiogenesis is essential for normal tissue and even more so for solid malignancies. At present, inhibition of tumor angiogenesis is a major focus of anticancer drug development. Bevacizumab, a humanized antibody against VEGF, was the first antiangiogenic agent to be approved for advanced non-small cell lung cancer, breast cancer and colorectal cancer. The most commonly observed adverse events are hypertension, proteinuria, bleeding and thrombosis. Sunitinib, a small molecule blocking intracellular VEGF, KIT, Flt3 and PDGF receptors, which regulate angiogenesis and cell growth, is approved for the treatment of advanced renal cell cancer (RCC) and malignant gastrointestinal stromal tumor. The most frequent adverse events include hand-foot syndrome, stomatitis, diarrhea, fatigue, hypothyroidism and hypertension. Sorafenib, an oral multikinase inhibitor, is approved for the second-line treatment of advanced RCC and upfront treatment of advanced hepatocellular carcinoma. Most common adverse events with sorafenib are dermatologic (hand-foot skin reaction, rash, desquamation), fatigue, diarrhea, nausea, hypothyroidism and hypertension. More recently, cardiovascular toxicity has increasingly been recognized as a potential adverse event associated with sunitinib and sorafenib treatment. Elderly patients are at increased risk of thromboembolic events when receiving bevacizumab, and potentially for cardiac dysfunction when receiving sunitinib or sorafenib. The safety of antiangiogenic drugs is of special concern when taking these agents for longer-term adjuvant or maintenance treatment. Furthermore, newer investigational antiangiogenic drugs are briefly reviewed.
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PMID:Antiangiogenic drugs in oncology: a focus on drug safety and the elderly - a mini-review. 1994 Apr 66

Vandetanib is an oral inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), epidermal growth factor receptor (EGFR) and Ret tyrosine kinases involved in tumor growth, progression and angiogenesis. Phase I studies indicated that the recommended dose of vandetanib as a single agent is 300 mg/day. Rash, diarrhea, hypertension and asymptomatic Q-Tc prolongation were the most common adverse events. Four randomized phase III clinical trials evaluated the efficacy of vandetanib in non-small cell lung cancer (NSCLC) in combination with docetaxel (ZODIAC), pemetrexed (ZEAL) or as a single agent (ZEST and ZEPHYR). Only the ZODIAC trial met its primary endpoint (progression-free survival [PFS]), while no study showed an advantage in overall survival with vandetanib. No significant antitumor activity has been observed in small cell lung cancer, advanced ovarian, colorectal, breast, prostate cancer and multiple myeloma. In advanced metastatic medullary thyroid cancer, one randomized phase III clinical trial has demonstrated that vandetanib can significantly improve response rate, PFS and time to worsening of pain. Several key questions remain to be addressed regarding the identification of clinical or molecular biomarkers predictive of response, the choice of the optimal dose or schedule of vandetanib and the safety of long-term administration. The results of ongoing trials in untreated patients with advanced NSCLC and other tumors should better define the optimal clinical application of vandetanib.
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PMID:Vandetanib: An overview of its clinical development in NSCLC and other tumors. 2096

Bevacizumab, a recombinant humanized monoclonal antibody targeting the vascular endothelial growth factor (VEGF), has been approved in the US as first- and second-line treatment of colorectal cancer and in the first-line treatment of advanced non-small cell lung cancer. The US FDA has also granted approval for the use of bevacizumab for the treatment of patients with metastatic renal cell carcinoma and glioblastoma, and in Europe, it is also approved in metastatic breast cancer in combination with paclitaxel. Bevacizumab is under investigation in the first-line and adjuvant setting of almost all types of solid tumors. However, anti-VEGF therapy is associated with significant toxicity. The incidence of grade 3-4 hypertension differs among the various malignancies in which bevacizumab is administered, possibly because of drug interactions with co-administered chemotherapy drugs. Hypertension appears to be dose dependent, and it is under investigation as a biomarker for VEGF inhibition efficacy. There are three main theories concerning the underlying pathophysiology: (i) the nitric oxide theory; (ii) the renal impairment theory; and (iii) the pre-eclampsia-like theory. The correct evaluation of the levels of hypertension is of critical importance and home blood pressure monitoring seems to be the most effective technique. A baseline assessment and follow-up monitoring of blood pressure is considered necessary for all patients receiving bevacizumab. There are no evidence-based recommendations regarding which antihypertensives are more appropriate for the management of bevacizumab-related hypertension. It has been suggested that the benefits from antihypertensive treatment are largely independent of the drugs used, as long as they adequately lower blood pressure. Randomized prospective studies are necessary to provide data that will be useful for the development of specific guidelines for the management of bevacizumab-related hypertension. In the meantime, treatment of anti-VEGF-induced hypertension should follow current guidelines for diagnosis and management of hypertension in general.
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PMID:Bevacizumab-induced hypertension: pathogenesis and management. 2162 40

Novel agents to reduce angiogenesis by targeting vascular endothelial growth factor and other proangiogenic signaling pathways are being developed for advanced nonsmall cell lung cancer. Antibody-based therapies (e.g., aflibercept) and multitargeted tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, and BIBF 1120) are being evaluated in phase III clinical trials. Some antiangiogenic agents have demonstrated distinct profiles in producing a variety of nonhematologic toxicities, including bleeding/hemorrhage, venous and arterial thromboembolic events, gastrointestinal perforation, hypertension, and proteinuria. Elucidating the molecular basis of these toxicities may lead to clinical benefits by improving patient selection and allowing for the development of effective prevention and management strategies.
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PMID:Antiangiogenic agents for the treatment of nonsmall cell lung cancer: characterizing the molecular basis for serious adverse events. 2174 83

Leptomeningeal metastasis is a devastating complication of advanced stage cancer. It is frequently accompanied by hydrocephalus and intracranial hypertension that must be treated by ventriculoperitoneal shunts. However, there are actual risks of peritoneal seeding or accumulation of malignant ascites after the cerebrospinal fluid diversion procedure, though it has not been reported. Here, we present the case of a patient with non-small cell lung cancer with leptomeningeal metastasis in whom malignant ascites developed after a subduroperitoneal shunt.
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PMID:Malignant ascites after subduroperitoneal shunt in a patient with leptomeningeal metastasis. 2220 24

Lung cancer is the leading cause of cancer-related death. Targeting the vascular endothelial growth factor (VEGF) pathways in combination with standard chemotherapy can improve response rate and survival in non-small cell lung cancer. Since October 2006, a new class of drugs targeting angiogenesis has been introduced for the treatment of advanced lung cancer. Bevacizumab, an antibody directly targeting VEGF was the first agent to be approved. Other small molecule tyrosine kinase inhibitors targeting the VEGF receptor are also active in the treatment of advanced lung cancer and are currently under development. Most of these new drugs are well tolerated though potentially significant toxicities such as haemoptysis and hypertension have been observed. This article will review these new-targeted anti-angiogenic agents with a focus on their use in lung cancer and on their important side effects.
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PMID:[Anti-angiogenic agents in the treatment of lung cancer: indications and toxicities]. 2240 11

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disorder involving mainly synovial joints. It can progress to a severely debilitating form with pulmonary, renal and cardiovascular involvement. Currently, disease-modifying antirheumatic drugs (DMARDs) remain the gold standard pharmacological therapy for RA (along with nonsteroidal anti-inflammatory drugs and corticosteroids). However, DMARDs are more or less ineffective in the late phase of the disease and adverse effects often limit their use. Studies show that serum levels of vascular endothelial growth factor (VEGF) remain elevated throughout the course of RA. In experimental models, the administration of pro-angiogenic cytokines, such as VEGF or FGF, has been shown to increase the severity of the disease. Therefore, anti-angiogenic drugs such as bevacizumab (which is already being used as an anti-tumor agent) may play a significant role in longstanding RA. However, adverse effects such as hypertension, gastro-intestinal perforation and the high cost of bevacizumab are major concerns. A recent study suggests that itraconazole, an antifungal drug, has a role in selectively inhibiting angiogenesis and growth of tumor in non-small cell lung cancer. Hence, this drug may be beneficial in the treatment of RA, especially in the later phase when other modalities have failed, or as an adjuvant. To test our hypothesis, we propose a randomized, double-blinded trial in patients with longstanding RA. The control group receives the standard DMARD therapy plus placebo, while the case group receives itraconazole in addition to DMARD therapy. Serum and synovial VEGF levels, in both the control group and the case group, are compared and their correlation with the symptoms is judged. If the VEGF levels are lower and/or the symptoms are less severe in the case group, our hypothesis will be confirmed. Multi-institutional efforts are needed to confirm this hypothesis, as it is relatively new and trial data is limited.
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PMID:Itraconazole: its possible role in inhibiting angiogenesis in rheumatoid arthritis. 2265 59

To evaluate the efficacy and safety of bevacizumab-containing chemotherapy for non-small cell lung cancer (NSCLC), we performed a population-based observational study. The efficacy and safety of bevacizumab-containing chemotherapy for NSCLC patients were evaluated at 14 sites (17 hospital departments) in a prefecture of Japan between December 2009 and August 2011. Complete data sets were obtained from 159 patients with NSCLC. The median age was 66 years, and 34.0 % of the patients were 70 years or older. The overall response rate to bevacizumab therapy was 41.6 %, and the disease control rate was 78.5 %. In 88 patients who received bevacizumab-containing chemotherapy as first-line therapy, the response and disease control rates were 55.0 and 78.9 %, respectively. The incidence of clinically significant (grade 3 or more) adverse events was generally low: proteinuria occurred in 2 (1.3 %) patients, hypertension in 2 (1.3 %), hemoptysis in 1 (0.6 %), and interstitial pneumonia in 1 (0.6 %). The time to treatment failure (TTF) in the 159 patients was 169 days, and the median overall survival (OS) was 580 days. In patients who received bevacizumab-containing chemotherapy as first-line therapy, the TTF and OS were 152 and 520 days, respectively. The difference in TTF between patients who received bevacizumab-containing chemotherapy as first-line therapy and those who received it as second-line or later-line therapy was not significant (p = 0.4971). With regard to first-line therapy, the difference in TTF between patients treated with carboplatin + pemetrexed + bevacizumab and those treated with carboplatin + paclitaxel + bevacizumab was not significant (p = 0.9435). We deduced that bevacizumab-containing chemotherapy is effective against NSCLC and also tolerable in clinical practice.
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PMID:Bevacizumab-containing chemotherapy for non-small cell lung cancer patients: a population-based observational study by the Ibaraki thoracic integrative (POSITIVE) research group. 2311 78


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