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)

Sunitinib, a new vascular endothelial growth factor receptor inhibitor, has demonstrated activity in renal cell carcinoma and is now widely used in the palliative treatment of patients with metastatic renal cell carcinoma. It is generally well tolerated but has been associated with a low incidence of grade 3 and 4 toxicities including fatigue, diarrhea, anorexia, mucositis, skin toxicity, immune thrombocytopenic purpura, hypertension, hypothyroidism, cytopenias, and decreased cardiac ejection fraction. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a rare condition that is severe and may be fatal. Several medications have been implicated in causing TTP-HUS including clopidogrel, mitomycin C, cisplatin. In this report, we describe a case of atypical HUS-microangiopathic hemolytic anemia during treatment with sunitinib in a patient with metastatic renal cell carcinoma. To our knowledge, this is the fourth case of microangiopathic hemolytic anemia associated with sunitinib described in the literature and the first case with fatal outcome despite treatment with plasmapheresis, dialysis, and withdrawal of sunitinib.
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PMID:Sunitinib-induced microangiopathic hemolytic anemia with fatal outcome. 2140 68

The multitargeted tyrosine-kinase inhibitor sunitinib has emerged as one of the standards of care for good- and intermediate-risk metastatic renal cell carcinoma. Although generally associated with acceptable toxicity, sunitinib exhibits a novel and distinct toxicity profile that requires monitoring and management. Fatigue, diarrhea, anorexia, oral changes, hand-foot syndrome and other skin toxicity, thyroid dysfunction, myelotoxicity, and hypertension seem to be the most common and clinically relevant toxicities of sunitinib. Drug dosing and treatment duration are correlated with response to treatment and survival. Treatment recommendations for hypertension have been published but, currently, no standard guidelines exist for the management of noncardiovascular side effects. To discuss the optimal management of noncardiovascular side effects, an international, interdisciplinary panel of experts gathered in November 2009. Existing literature on incidence, severity, and underlying mechanisms of side effects as well as on potential treatment options were carefully reviewed and discussed. On the basis of these proceedings and the thorough review of the existing literature, recommendations were made for the monitoring, prevention, and treatment of the most common noncardiovascular side effects and are summarized in this review. The proactive assessment and consistent and timely management of sunitinib-related side effects are critical to ensure optimal treatment benefit by allowing appropriate drug dosing and prolonged treatment periods.
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PMID:Sunitinib in metastatic renal cell carcinoma: recommendations for management of noncardiovascular toxicities. 2149 Jan 27

A 14-year-old girl with metastatic renal cell carcinoma was treated with nephrectomy, interferon, and several lines of the targeted agents sorafenib, bevacizumab, sunitinib, and everolimus, either alone or in combination. Treatment was well tolerated, but the patient developed hypothyroidism and significant hypertension with bevacizumab and sunitinib. She responded to all agents and was given radiation treatment twice at the time of symptomatic disease progression; she died 33 months from diagnosis.
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PMID:Continuing response to subsequent treatment lines with tyrosine kinase inhibitors in an adolescent with metastatic renal cell carcinoma. 2155 43

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

Chemotherapy has little impact on renal carcinoma. Interferon alfa is the standard treatment, in the absence of a better alternative, but the median survival time is less than a year among patients with advanced-stage or metastatic disease. Pazopanib inhibits multiple receptor tyrosine kinases, including the tyrosine kinase coupled to the vascular endothelial growth factor receptor (VEGFR), thus inhibiting angiogenesis. It is authorised in the European Union for the treatment of advanced-stage renal carcinoma. Clinical evaluation of pazopanib is based on a double-blind placebo-controlled trial in 435 patients. Follow-up is currently too short to determine whether pazopanib improves overall survival. The median progression-free survival time, based on radiological criteria, was 5 months longer with pazopanib: 9.2 months versus 4.2 months with placebo. This is similar to the efficacy obtained in trials of other cytotoxic drugs such as sunitinib. The adverse-effect profile of pazopanib is unfavourable: it includes disorders linked to its antiangiogenic activity (hypertension, arterial thrombosis, myocardial infarction, haemorrhage, etc.), as well as gastrointestinal disorders and hand-foot syndrome. In clinical trials including a total of 593 patients, 2 patients receiving pazopanib developed torsades de pointes and 3 other patients died of liver failure. Numerous pharmacokinetic interactions are likely, notably involving cytochrome P450 isoenzyme CYP 3A4. The risk-benefit balance of pazopanib is currently too unfavourable to justify its use in patients with advanced-stage or metastatic kidney cancer.
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PMID:Pazopanib. Kidney cancer: many risks, but is there a benefit for patients? 2164 24

Targeted antiangiogenic cancer therapies have revolutionized the treatment of highly vascularized cancers such as metastatic renal cell carcinoma and gastrointestinal stromal tumors. Such agents act by inhibiting the actions of proangiogenic growth factors and their receptor tyrosine kinases, which are known to be overexpressed in cancer. However, these factors also play an important role in normal cardiovascular physiology. This article summarizes the incidences of cardiovascular toxicities (namely hypertension and heart failure) associated with the most commonly used antiangiogenic therapies, and then presents data from preclinical and clinical studies to provide some insight into the underlying molecular mechanisms.
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PMID:Molecular mechanisms of hypertension and heart failure due to antiangiogenic cancer therapies. 2174 82

Multiple molecularly targeted agents (MTAs) have been approved for the management of metastatic renal cell carcinoma (mRCC). Sunitinib and mammalian target of rapamycin inhibitors (temsirolimus, everolimus) are primarily metabolized in the liver, whereas the metabolism of bevacizumab is unclear. There are limited data on the toxicity profile and the efficacy of these agents in patients with renal insufficiency (RI). This is clinically relevant, especially as about one-third of patients with mRCC have renal dysfunction. The primary objective was to assess the safety and efficacy of targeted agents in patients with mRCC with RI. Medical records of patients with mRCC at Wayne State University, started on sunitinib, temsirolimus, everolimus, or bevacizumab, were reviewed. Patients with a calculated creatinine clearance of less than or equal to 60 ml/min were deemed to have RI. Data on safety and efficacy of MTA therapy were collected and analyzed with respect to renal function. RI was observed in 33% of our patients with mRCC. The incidence of toxicities, responses, time to progression, and overall survival were not significantly different in patients with RI compared with patients with normal renal function. Patients with RI had larger median increases in blood pressure with sunitinib and bevacizumab, increased incidence of thyroid dysfunction with sunitinib, and increased incidence of rash and dose interruptions with mammalian target of rapamycin inhibitors, than did patients with normal renal function. In conclusion, RI was commonly observed in our patients with mRCC. Molecularly targeted agents are well tolerated, and efficacy seems to be maintained in patients with RI. Vigilant monitoring of hypertension would be recommended for patients receiving sunitinib and bevacizumab.
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PMID:Safety and efficacy of molecularly targeted agents in patients with metastatic kidney cancer with renal dysfunction. 2179 72

The introduction of angiogenesis inhibitors has altered the systemic therapy of metastatic renal cell carcinoma. Being a"permanent" medication, the management of side effects has special importance, for adverse events may limit therapy. Hypertension (up to 34% of cases) and palmar plantar erythroderma (6-30% of cases) are common side effects.Blood pressure should be monitored during therapy, and arterial hypertension should be treated with a standard medication. If a hypertensive emergency still occurs, a dose reduction or discontinuation of treatment might be indicated.Prophylaxis may prevent or extenuate palmar plantar erythroderma in many cases, enabling regular chemotherapy as planned. In cases with severe clinical symptoms a reduction or interruption of the dose will be necessary. In most cases local therapy is sufficient.
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PMID:[Hypertension and palmar plantar erythroderma. Management of adverse events of angiogenetic inhibitors in the treatment of renal cell carcinoma]. 2180 Jan 97

The targeted therapies available to treat metastatic kidney cancer include vascular endothelial growth factor (VEGF) inhibitors, bevacizumab, sorafenib, sunitinib, pazopanib, and the mTor inhibitors temsirolimus and everolimus. These agents have significantly improved patient outcomes but are associated with toxicities. The most common toxicities seen with the VEGF inhibitors are hypertension, fatigue, and hand- foot syndrome. The mTor inhibitors exhibit a different toxicity profile which includes hyperglycemia and hypertriglyceridemia. Recognition and understanding the mechanism of the toxicities is crucial for optimal patient management.
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PMID:Toxicities of targeted agents in advanced renal cell carcinoma. 2182 92

The rapid evolution of targeted therapies has had a dramatic impact on multiple domains in oncology, particularly metastatic renal cell carcinoma (RCC). Four agents antagonizing vascular endothelial growth factor-mediated signaling have been approved for the treatment of metastatic RCC, including the monoclonal antibody bevacizumab and the small molecular inhibitors sunitinib, sorafenib, and pazopanib. Pazopanib was approved in 2009 for this disease on the basis of a phase III clinical trial demonstrating a superior progression-free survival compared to placebo in 435 patients with either treatment-naive or cytokine-refractory disease. The trial offered insight related to the toxicity profile associated with this agent. The most common clinical adverse events are diarrhea, hypertension, nausea, anorexia, and vomiting. With respect to laboratory adverse events, hepatotoxicity represents a specific concern with pazopanib. Oncology nurses play a critical role in counseling patients regarding the toxicity profile and management of adverse events in pazopanib treatment.
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PMID:Nursing considerations with pazopanib therapy: focus on metastatic renal cell carcinoma. 2195 37


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