Mechanism of Action
Bevacizumab(Drug information on bevacizumab) binds to (VEGF) so that it cannot bind to its receptors Flt-1 and KDR on the endothelial cell surface. Normally, VEGF would bind to these receptors and stimulate the endothelial cells to proliferate and migrate to the tumor to develop a new blood supply for the tumor. Tumors are unable to grow beyond 1–2 mm, the diffusion distance of oxygen, without having new blood vessels to bring in oxygen and remove cellular waste products. It is theorized that bevacizumab, in combination with chemotherapy, normalizes tumor blood vessels so that concomitantly administered chemotherapy can enter and reach all parts of the tumor to exert an antitumor effect. Malignant blood vessels are tortuous, with many blind endings and different diameters, so some areas of the tumor receive little, if any, blood supply, and the vasculature has holes, or fenestrations, through which drugs leak out of the tumor.
Drug serum half-life is approximately 20 days (range, 11–50 days), with a predicted time to steady state of 100 days. Drug clearance is higher in males and patients with a higher tumor burden, but there is no evidence that this results in inferior responses.
Drug is available in single-use 4 mL 100-mg vials and in
16 mL 400-mg vials.
Aseptically withdraw ordered dose from appropriate vial(s) and dilute to a total volume of 100 mL 0.9% Sodium Chloride(Drug information on sodium chloride) Injection USP. Discard any remaining drug, as it has no preservatives.
Administer initial infusion over a period of 90 minutes; administer subsequent infusions over a 60-minute time period if the initial infusion is well tolerated, and all subsequent infusions over a 30-minute period if the second 60-minute infusion is well tolerated. Do not administer intravenous push (IVP) or intravenous (IV) bolus.
Initiate bevacizumab at least 28 days following major surgery and after surgical wound is fully healed. Reidy et al. demonstrated that bevacizumab 5 mg/kg could be safely administered at 0.5 mg/kg/min (10 minutes). Three hundred seventy patients received a total of 2,311 doses with 1.6% of patients developing symptoms of mild hypersensitivity reactions. This dosage is not recommended by the manufacturer, however.