Hypertension bevacizumab

The pharmacokinetics of bevacizumab demonstrate a terminal half-life of 21 days, with a volume of distribution consistent with limited extravascular distribution.34 Bevacizumab has shown clinical activity in the treatment of colorectal, kidney, lung, breast, and head and neck cancer. Patients may develop hypertension requiring chronic medication during therapy. Impaired wound healing, thrombolembolic events, proteinuria, bleeding, and perforation are serious side effects. 

Bevacizumab 10 mg/kg IV on days 1 and 15, cycled every 28 days (paclitaxel 90 mg/m2 IV on days 1, 8 and 15) Hypertension, gastrointestinal perforation, impaired wound healing, bleeding, thromboembolic events, proteinuria... 

Bevacizumab is a humanized monoclonal antibody directed against vascular endothelial growth factor. Bevacizumab is associated with hypertension, which is easily managed with oral antihypertensive agents. 

Hypertension, thrombosis, proteinuria from bevacizumab added to toxicities of regimen chosen... 

Patients should be closely monitored for side effects that require aggressive intervention such as irinotecan-induced diarrhea and bevacizumab-induced GI perforation. Patients should be evaluated for other treatment-specific side effects such as oxaliplatin-induced neuropathy, cetuximab and panitumumab-induced skin rash, and bevacizumab-induced hypertension and proteinuria. 

Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor. It should be used with caution in patients with a history of hypertension because of an increased risk of proteinuria and in patients with uncontrolled hypertension. Side-effects that may be expected include... 

The serious adverse effects associated with bevacizumab include GI perforation, hemorrhage, hypertension, complications in wound healing, nephritic syndrome, congestive heart failure and arterial thromboembolic events. Patients receiving bevacizumab commonly experience pain, asthenia, headache, abdominal pain, nausea, vomiting, anorexia, upper respiratory infection and exfoliative dermatitis. 

Bevacizumab [Avastin] Colorectal carcinoma Hemorrhage hypertension Gl distress [nausea, vomiting, diarrhea] blood disorders [leukopenia, neutropenia] others... 

The most frequent adverse events encountered under treatment with sunitib are hypertension (18 to 28% ) and asthenia (42 to 47% ). In two Phase It studies in patients with metastatic renal carcinoma, hypertension has been noted in 48 patients out of 169 (28% ), with 6% presenting with a grade 3 hypertension versus 1% of patients receiving placebo. No grade 4 hypertension has been reported and dosage reduction or withdrawal of treatment allowed blood pressure control [219,223]. The mean time before apparition of hypertension was 131 days [7 - 316] after bevacizumab first dose. Moreover, 12% of those patients from this study had elevation of their serum creatinine. 

Mares, JE, Worah, S, Mathew, SV. Increased rates of hypertension (HTN) among patients with advanced carcinoid treated with bevacizumab. the 41 st Annual Meeting of the American Society of Clinical Oncology (ASCO).Abstract No 4087, 2005. 

Martel CL (2006) Bevacizumab-related toxicities Association of hypertension and proteinuria. Commun Oncol 3 90-93... 

Bevacizumab Inhibition of angiogenesis/ neovascularization 5 mg/kg IV every 14 days until disease progression Hypertension pulmonary hemorrhage gastrointestinal perforation proteinuria congestive heart failure... 

Observational studies In a prospective study of bevacizumab combined with chemotherapy for first-line treatment of metastatic colorectal cancer, bevacizumab-related adverse events were gastrointestinal perforation (1.9%), arterial thromboembolic events (2%), grade 3—4 bleeding (2.2%), and de novo hypertension requiring medication (22%) [81 =]. 

Bevacizumab plus first-line chemotherapy has been evaluated in the Bevacizumab Expanded Access Trial (BEAT) in patients with unresectable metastatic colorectal cancer [82 ]. The serious/grade 3-5 adverse events with bevacizumab included hypertension (5.3%), bleeding (3%), gastrointestinal perforation (2%), arterial thromboembolism (1%), proteinuria (1%), and wound-healing complications (1%). 

In a phase II trial of bevacizumab with dacarbazine and daily low-dose interferon alfa-2a as first-line treatment in 26 patients with metastatic melanoma, there were four life-threatening adverse events pulmonary thromboembolism (n = 2), intracerebral hemorrhage (n = l), and grade 4 hypertension ( = 1). In two cases the event occurred at least 3 months after the last dose [86 ]. 

Cardiovascular Hypertension was common in a retrospective chart review of patients with colorectal cancers treated with bevacizumab 21% developed grade 3 hypertension, 14% grade 2 hypertension, and 7% grade 1 hypertension [89 ]. 

There was an increased risk of high-grade hypertension with bevacizumab in patients with a variety of tumors in a meta-analysis of 20 studies in 12 656 patients [90 ]. The risk may be dose-related and vary with tumor type, as shown by another metaanalysis [91 ]. 

In a meta-analysis of all prospective phase I-III trials published up to December 2008 of bevacizumab, grade 3-4 hypertension occurred in 9.2%, grade 3-4 left ventricular systolic dysfunction in 0.3%, and grade 3-4 thromboembolism in 9.6% [92 ]. 

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