Introduction to Bevacizumab

Bevacizumab (trade name Avastin) is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor A (VEGF-A). It was first approved by the FDA in 2004 for the treatment of metastatic colorectal cancer and has since been approved for various other cancers in adults. In pediatrics, its use is primarily in research settings and for specific off-label indications.

Mechanism of Action

Bevacizumab works by:

• Binding to VEGF-A, preventing it from interacting with its receptors (VEGFR-1 and VEGFR-2) on the surface of endothelial cells
• Inhibiting new blood vessel formation (angiogenesis), which is crucial for tumor growth and metastasis
• Causing regression of existing tumor vasculature
• Normalizing tumor vasculature, potentially improving delivery of other anti-cancer therapies

Clinical Applications

In pediatrics, bevacizumab is used primarily in research settings and for off-label indications, including:

• Recurrent or progressive high-grade gliomas
• Diffuse intrinsic pontine glioma (DIPG)
• Retinopathy of prematurity (ROP)
• Neurofibromatosis type 2 (NF2)-associated vestibular schwannomas
• Recurrent or metastatic soft tissue sarcomas

It's important to note that many of these uses are based on limited evidence and ongoing clinical trials.

Dosage and Administration

Dosing in pediatrics is often extrapolated from adult studies and may vary based on the specific condition being treated. Common dosing regimens include:

• 10 mg/kg IV every 2 weeks
• 15 mg/kg IV every 3 weeks

Administration:

• Given as an intravenous infusion
• Initial infusion over 90 minutes; if well-tolerated, subsequent infusions can be given over 60 or 30 minutes
• Should not be administered as an IV push or bolus

Adverse Effects

Common adverse effects include:

• Hypertension
• Proteinuria
• Impaired wound healing
• Hemorrhage
• Thromboembolism
• Reversible posterior leukoencephalopathy syndrome (RPLS)

Rare but serious adverse effects:

• Gastrointestinal perforation
• Arterial thromboembolic events
• Osteonecrosis of the jaw
• Congestive heart failure

Considerations in Pediatrics

When using bevacizumab in pediatric patients, consider:

• Limited data on long-term effects in developing organs
• Potential impact on growth plate function and bone development
• Need for close monitoring of blood pressure and proteinuria
• Importance of dental evaluation before initiation due to risk of osteonecrosis of the jaw
• Contraindication in pregnancy - relevant for adolescent patients