Bevacizumab

Bevacizumab (Avastin) is a recombinant, humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). VEGF is a proangiogenic growth factor found in many cancers including colorectal and is thought to promote blood vessel formation and metastasis of the tumor by binding to VEGF receptors on tumors.

Bevacizumab inhibits circulating VEGF, preventing it from binding to receptors and

decreasing the formation of new blood vessels. Additionally, bevacizumab may allow for increased concentrations of traditional chemotherapy such as irinotecan to reach the tumor to exert its pharmacologic effect. Bevacizumab is not effective alone and must be used in combination with other agents effective in colorectal cancer. It is indicated for first-line treatment of patients with metastatic colorectal cancer in combination with IV 5-fluorouracil-based regimens. Bevacizumab has also been shown to increase survival in the second-line setting when used in combination with the FOLFOX regimen in patients who have not yet received bevacizumab.41

Adverse effects associated with bevacizumab include hypertension which is com-

38,50

mon but easily managed with oral antihypertensive agents. ' Thrombotic events (including myocardial infarctions, pulmonary embolisms, and deep vein thrombosis) occur more frequently in the elderly patients with cardiovascular risk factors and need to be monitored routinely. Because bevacizumab interferes with normal wound healing, it should not be given shortly before or after surgical procedures.50 Initiation within 28 days of surgery is not recommended to allow for proper wound healing and decrease the risk of bleeding. The amount of time needed after bevacizumab discontinuation to perform elective surgical procedures is less clear but health care providers should take into consideration bevacizumab's half-life of approximately 20 days when making clinical decisions.50 Patients should have their urine checked for protein prior to each dose of bevacizumab to check for potential kidney damage. Patients who have developed 2+ protein on the urinalysis require additional testing prior to receiving therapy. These patients will have their 24-hour urine collected and assessed for protein. Therapy is interrupted for 2 g or more of proteinuria/24 hours and resumed when proteinuria was less than 2 g/24 hours. Finally, there is a risk of GI perforation that is rare but potentially fatal. Patients complaining of abdominal pain associated with vomiting or constipation should be counseled to call their physician immediately. Bevacizumab is commonly given at a dose of 5 mg/kg IV every 14 days until disease progression. Once disease progresses and salvage chemotherapy is initiated, the benefit of continuing bevacizumab is unclear.

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