Bevacizumab

From Ganfyd

Bevacizumab is a humanised monoclonal antibody against vascular endothelial growth factor (VEGF). VEGF-mediated angiogenesis is thought to sustain the growth of many cancers and this is the rationale behind targetting VEGF. It is also a promising drug in treating proliferative diabetic retinopathy^[1] and wet macular degeneration by intraocular injection, which is cheaper than Ranibizumab and may offer lower toxicity than that of systemic administration where it also works ^[2]. It appears to have cardiovascular complications long term when given systemically. A recombinant monoclonal antibody.

Indication

• Licensed for metastatic carcinoma of the colon or rectum.
• Combination with interferon alfa-2a in renal cell cancer
• There has been use for intravitreal use of bevacizumab wet age-related macular degeneration but the drug is not licensed for this indication and there is no evidence that the license holder intends to sponsor the studies necessary for this to occur. Independent evidence is however accumulating on safety^[3] and efficacy in a number of intraocular indications. ^[4][5][6][7]. It has a higher molecular weight than licensed alternatives meaning it is theoretically less likely to cause systemic side-effects and in intravitreal use has a relatively long half life of 5-10 days. The difference in properties may be important but this needs further study and could go either way in terms of net benefit^[8]. Bevacizumab and ranibizumab use was not associated with increased risks of mortality, myocardial infarction, bleeding, or stroke compared with photodynamic therapy or pegaptanib^[9]. Ranibizumab may be safer with respect to arterial thrombotic events and severe intraocular inflammation than bevacizumab^[10].

Increasingly this is becoming the default commissioned anti-VGEF agent in the NHS for ocular indications on resource effectiveness grounds^[11]

Negative indications

The FDA began in late 2010 the procedure to withdraw it for breast cancer as the promise of an initial trial was followed by two subsequent trials with worse outcome^[12]. The process of withdrawal was completed in November 2011

Possible indications

Any condition associated with tissue proliferation.

• Malignancies
• Rubeosis
• Ocular venous occlusive disease
• Cystoid macular oedema
• Proliferative diabetic retinopathy
• Vitreous haemorrhage
• Retinopathy of prematurity^[13]

Contraindications

• Pregnancy
• CNS metastases
• Hypersensitivity

Side-effects

• Hypertension
• Heart failure
• Gastrointestinal perforation
• Proteinuria
• Arterial thromboembolism
• Haemorrhage
• Neutropenia

References