Angiogenesis inhibitor approved as part of combination therapy for first-line treatment of nonsquamous NSCLC
BevacizumabGENENTECHAngiogenesis inhibitor approved as part of combination therapy for first-line treatment of nonsquamous NSCLC
This monoclonal antibody binds human vascular endothelial growth factor (VEGF), preventing VEGF from binding with its receptors. The inhibition of binding prevents the proliferation of endothelial cells and the formation of new blood vessels, and this angiogenesis inhibition slows microvascular growth and metastatic progression. Bevacizumab, in combination with carboplatin and paclitaxel, was approved on October 12, 2006, for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic nonsquamous, non-small cell lung cancer (NSCLC). Bevacizumab was previously approved as part of combination therapy for the treatment of patients with metastatic carcinoma of the colon or rectum.
Safety. Cases of gastrointestinal perforations with associated fistula formation or intra-abdominal abscesses have been reported; some cases have been fatal. In patients with gastrointestinal perforation, bevacizumab should be permanently discontinued. Bevacizumab therapy can lead to complications in wound healing, including wound dehiscence. Patients should not begin treatment with bevacizumab until ≥28 days have elapsed since major surgery and surgical incisions have fully healed. Patients treated with bevacizumab have experienced both minor hemorrhages and serious, sometimes fatal, hemorrhagic events. In patients with serious hemorrhage, bevacizumab therapy should be discontinued. Bevacizumab therapy may lead to arterial thromboembolic events, including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina. Severe hypertension also has been reported among patients treated with bevacizumab. Bevacizumab therapy has been associated with severe neutropenia, febrile neutropenia, proteinuria, reversible posterior leukoencephalopathy syndrome, and congestive heart failure. Infusion reactions reported in clinical trials include hypertension, hypertensive crises, wheezing, oxygen desaturation, hypersensitivity, chest pain, headaches, rigors, and diaphoresis. The most common adverse events associated with bevacizumab treatment include asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis, and proteinuria.
Dosing. The recommended dose of bevacizumab is 15 mg/kg as an intravenous infusion every 3 weeks. The initial dose should be delivered over 90 minutes, with the infusion time dropping to 60 minutes and then to 30 minutes at subsequent infusions if the infusion time is well tolerated.