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)

PURPOSE Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF) with demonstrated efficacy in combination with carboplatin and paclitaxel (PCB) for the treatment of advanced non-small-cell lung cancer (NSCLC). Administration of bevacizumab is postulated to decrease nitric oxide synthesis and lead to hypertension, which may be a physiological sign that the VEGF pathway is more actively being blocked and could result in improved outcomes. PATIENTS AND METHODS Eastern Cooperative Oncology Group (ECOG) 4599 randomly assigned patients with nonsquamous NSCLC to carboplatin and paclitaxel (PC) versus PCB. Hypertensive patients were compared with nonhypertensive patients with respect to overall survival (OS) and progression-free survival (PFS) using blood pressure data and adverse event data separately. High blood pressure (HBP) by the end of cycle 1 was defined as blood pressure > 150/100 at any previous time or at least a 20-mmHg increase in diastolic blood pressure from baseline. Results In a multivariable Cox model adjusting for HBP as a time-varying covariate, comparing those on PCB with HBP with those on PC gave an OS hazard ratio (HR) of 0.60 (95% CI, 0.43 to 0.81; P = .001); comparing those on PCB without HBP with those on PC alone, the OS HR was 0.86 (95% CI, 0.74 to 1.00; P = .05). Comparing the PCB HBP group with PC gave an adjusted PFS HR of 0.54 (95% CI, 0.41 to 0.73; P < .0001) and comparing those on PCB without HBP to those on PC, the HR was 0.72 (95% CI, 0.62 to 0.84; P < .0001). The 6-month cumulative incidence of hypertension was 6.2% (95% CI, 3.9% to 8.6%). CONCLUSION Data from ECOG 4599 suggest that onset of HBP during treatment with PCB may be associated with improved outcomes, and additional studies of the downstream effects of VEGF suppression and hypertension are needed.
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PMID:Clinical course of advanced non-small-cell lung cancer patients experiencing hypertension during treatment with bevacizumab in combination with carboplatin and paclitaxel on ECOG 4599. 2008 37

Colorectal cancer continues to be an important public health concern, despite improvements in screening and better systemic chemotherapy. The integration of targeted therapies in the treatment of colon cancer has resulted in significant improvements in efficacy outcomes. Angiogenesis is important for tumor growth and metastasis and is an important target for new biological agents. Bevacizumab is a humanized recombinant antibody that prevents vascular endothelial growth factor (VEGF) receptor binding, and inhibits angiogenesis and tumor growth. The addition of bevacizumab to fluoropyrimidine-based chemotherapy, with or without irinotecan or oxaliplatin, in both the first- and second-line treatment of metastatic colorectal cancer, significantly increased median progression-free survival and overall survival in select randomized phase III studies. Ongoing studies are evaluating the role of bevacizumab in the adjuvant treatment of colon cancer. Common toxicities associated with bevacizumab include hypertension, bleeding episodes, and thrombotic events. This review will focus on the integration of bevacizumab in the treatment paradigm of colon cancer and the management of its side effects.
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PMID:Targeted therapies in the management of colorectal carcinoma: role of bevacizumab. 2061 90

Primary spinal cord tumors constitute 2-4% of all primary central nervous system malignancies in adults of which less than 5% are glioblastoma. A retrospective evaluation to determine toxicity and response to bevacizumab in patients with recurrent spinal cord glioblastoma. Six patients (4 males; 2 females: median age 34 years) with recurrent spinal cord glioblastoma were treated with bevacizumab (10 mg/kg given once every 2 weeks wherein 2 treatments constituted a cycle of therapy). All patients had failed surgery and temozolomide-based chemoradiotherapy and post-radiotherapy temozolomide. Blood counts, chemistry panel, urine protein to creatinine ratio and neurologic examination were obtained bi-weekly. Contrast-enhanced spine MRI was performed after one cycle of therapy and thereafter following every two cycles of bevacizumab. Treatment-related complications included fatigue in six patients, constipation in 4, hypertension in 2, venous thrombosis in 2, and infection without neutropenia in 2. There were three grade 3 toxicities (1 each fatigue, leukopenia and venous thrombosis). There were no treatment-related deaths. After one cycle of bevacizumab, one patient (17%) demonstrated progressive disease, 2 (34%) partial responses and three (51%) stable disease. Overall median response or stable disease duration (disease free progression) was 7 months (range 3-11 months). Overall median survival was 9 months (range of 5-13 months). Bevacizumab is well tolerated, has tolerable toxicity and apparent activity in this small cohort of adults with recurrent spinal cord glioblastoma.
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PMID:Recurrent spinal cord glioblastoma: salvage therapy with bevacizumab. 2068 Mar 97

The nephrotoxicity of some cancer drugs is well known. Given the rapid development of cancer research, careful assessment of patients treated with new drugs, which may have new toxicity profiles, is mandatory. The nephrotoxicity of cisplatin is likely due to inhibition of autophagy priming, while that of methotrexate is related to direct tubular toxicity and intratubular precipitation. Both can be prevented by adequate hydration. The mechanism of radiation nephropathy development is unclear, but chronic oxidative stress and inflammation seem to play a key role. Mesangiolysis is a characteristic feature, followed by vascular alterations, atrophy, fibrosis, and necrosis. Inhibitors of vascular endothelial growth factor (VEGF), such as bevacizumab, sunitinib, and sorafenib, interfere with angiogenesis. Bevacizumab is a humanized monoclonal antibody which binds to circulating VEGF. Sunitinib and sorafenib are small molecules inhibiting tyrosine kinase of the intracellular domain of the VEGF receptor. Treatment with anti-VEGF drugs is frequently complicated by proteinuria, acute renal failure, and hypertension. The most frequent histological lesion is thrombotic microangiopathy. Inhibitors of the BCR-Abl tyrosine kinase domain on the Philadelphia chromosome (imatinib, nilotinib and dasatinib) may cause acute renal failure.
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PMID:[Cancer treatment-induced nephrotoxicity: BCR-Abl and VEGF inhibitors]. 2092 99

The purpose of this preliminary study was to retrospectively assess the incidence of bowel perforation and hypertension in two separate advanced ovarian cancer patient populations following first-line therapy, comprising paclitaxel, carboplatin and bevacizumab. The first 20 patients were treated with six cycles of paclitaxel (175 mg/m2), carboplatin (AUC of 5 i.v.), and bevacizumab (15 mg/kg of body weight); q21 days per an independent protocol. The subsequent patients (n = 12) were administered weekly paclitaxel (80 mg/m2), carboplatin (AUC of 5 i.v.) every four weeks, and bevacizumab (10 mg/kg of body weight) every two weeks for six cycles according to a separate, independent protocol. Bevacizumab was not added to either chemotherapy regimen until cycle 2. In both groups patients who achieved a complete response, partial response or stable disease at the conclusion of induction therapy received bevacizumab (10 mg/kg) and paclitaxel (135 mg/m2) q21 days as maintenance therapy. A total of 170 cycles (median = 6; range 3-6) of primary induction chemotherapy, 140 of which contained bevacizumab, were administered. Moreover, 206 cycles (median = 9; range 1-12) of maintenance chemotherapy have been delivered to 28 patients thus far. There was no incidence of GI perforation and only two patients demonstrated clinically significant hypertension. Previous studies involving bevacizumab have raised concerns regarding bowel perforations and hypertension. However, we did not encounter difficulties with either of these complications. While we recognize that the risk for bowel perforation remains in the 5-11% range, the study's preliminary results suggest that first-line treatment of advanced stage ovarian carcinoma with bevacizumab can be safely administered.
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PMID:Bevacizumab, paclitaxel and carboplatin for advanced ovarian cancer: low risk of gastrointestinal and cardiovascular toxicity. 2107 75

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor that has antiangiogenic activity and improves progression-free survival in many solid malignancies when combined with cytotoxic chemotherapy, but has little effect on overall survival. Despite the effects of this drug in unselected patients, the Response Evaluation Criteria in Solid Tumours are suboptimum to predict benefit. Additionally, tumours show inherent and emerging resistance to regimens that include bevacizumab. The ability to target therapy towards well selected subgroups of patients would increase the likelihood of benefits and would improve cost-effectiveness and therapeutic outcomes. In this review we discuss putative clinical, radiological, and molecular markers of bevacizumab efficacy, derived from data obtained in clinical trials. Current evidence indicates some predictive value for hypertension, vascular imaging, and polymorphisms affecting components of the vascular endothelial growth factor pathway in patients receiving bevacizumab. Many questions relating to these and other surrogate biomarkers, however, remain unanswered and their clinical usefulness has yet to be proven.
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PMID:Biomarkers to predict the clinical efficacy of bevacizumab in cancer. 2137 89

Bevacizumab (BV) is widely used for patients with metastatic colorectal cancer. We investigated the efficacy and safety of chemotherapy combined with BV for metastatic colorectal cancer. From July 2007 to October 2008, 59 patients were treated by chemotherapy with BV in our hospital. Of the 47 patients who received BV in first-line therapy, 3 cases (6%) with complete response (CR), 25 cases(53%) with partial response (PR), and 17 cases (36%) with stable disease (SD) were observed. The overall response rate and tumor control rate were 60% and 96%, respectively. The median progression-free survival (PFS) was 11. 9 months, and median overall survival (OS) was 23. 6 months. There were 12 patients treated first with BV in second-line therapy. Of the 12 patients, 1 case (8%) with CR, 3 cases (25%) with PR, and 4 (33%) with SD were observed. The overall response rate and tumor control rate were 33% and 67%, respectively. The median PFS was 6.0 months and median OS was not reached. With regard to the grade 3 to 4 adverse events by NCI-CTCAE ver3.0, neutropenia was observed in more than half of the patients (56%), but a few of patients had gastrointestinal toxicities, peripheral neuropathy and infections in non-hematologic toxicities. BV-associated adverse events were hypertension, proteinuria, venous thrombosis, wound healing complication, gastrointestinal perforation and bleeding, each of which were few and not serious. Six of the patients experienced PD after first-line therapy treated with BV continuously in second-line therapy. Four of six were surviving without disease progression at the last follow-up, which suggests the effectiveness of continuation of BV. Our study showed the efficacy and safety of BV for metastatic colorectal cancer.
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PMID:[Efficacy of chemotherapy combined with bevacizumab for metastatic colorectal cancer]. 2136 62

Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, has been widely used in a variety of malignancies offering substantial clinical benefit. Hypertension and proteinuria are the most commonly reported manifestations of bevacizumab-related nephrotoxicity with the risk increasing along with the dose and with the concomitant use of bisphosphonates. We describe the first case of a patient with small-cell lung cancer who developed diffuse extracapillary necrotizing crescentic glomerulonephritis, temporarily necessitating haemodialysis, following administration of bevacizumab and zolendronate. Renal function improved without any specific treatment and the patient remained off dialysis after withdrawal of bevacizumab-zolendronate. Special caution is required when VEGF inhibitors are combined with bisphosphonates. Such a combination can cause crescentic necrotizing glomerular lesions. Withdrawal of the offending medications may be adequate for the alleviation of this severe glomerulonephritis.
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PMID:Crescentic glomerulonephritis associated with vascular endothelial growth factor (VEGF) inhibitor and bisphosphonate administration. 2138 92

Bevacizumab, which is a humanized monoclonal antibody against vascular endothelial growth factor, is used to treat metastatic cancers of the colon. Adverse effects common with bevacizumab treatment are hypertension, arterial-venous thrombosis, bleeding, gastrointestinal perforation, and proteinuria. To date, there have been no reports of refractory seizure following treatment with bevacizumab. We describe a patient who presented with refractory generalized tonic-clonic seizures after receiving last dose of bevacizumab for treatment of metastatic colorectal cancer with FOLFIRI and bevacizumab regimen.
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PMID:Refractory generalized seizures as a possible side effect of bevacizumab in a colon cancer patient. 2146 80

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


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