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Bevacizumab: Indications, Adverse Effects, Contraindications, and Dosage

Mechanism of action of bevacizumab:

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor (VEGF). It inhibits angiogenesis and thereby suppresses tumor growth.

Urologic indications for bevacizumab:

Bevacizumab was an option for first-line treatment of metastatic renal cell carcinoma in combination with interferon alfa-2a. In combination with interferon, bevacizumab prolonged progression-free survival (PFS) to 10.2 months versus 5.4 months compared with interferon monotherapy (Escudier et al., 2007; Motzer & Bukowski, 2006). As immune checkpoint inhibition has become the standard of care for metastatic renal cell carcinoma, bevacizumab is now used only rarely (e.g., when checkpoint inhibitor therapy is contraindicated).

Pharmacokinetics of Bevacizumab:

Intravenous administration: the initial infusion over 90 minutes; if well tolerated, the second infusion over 60 minutes; all subsequent infusions over 30 minutes. The drug undergoes proteolytic catabolism in the body; elimination half-life is approximately 18–20 days.

Adverse Effects of Bevacizumab:

Gastrointestinal tract:

Very common: diarrhea. Common: abdominal pain, constipation, stomatitis. Serious but uncommon: intestinal perforation, fistulas.

Respiratory:

Very common: dyspnea. Common: epistaxis. Pulmonary embolism

Vascular:

Very common: hypertension. Common: bleeding; thromboembolic events 2%.

Kidney:

Very common: proteinuria. Nephrotic syndrome (1%).

Skin:

Common: rash, xerosis.

Other:

Very common: asthenia and fatigue.

Contraindications to bevacizumab:

Allergy, pregnancy, one month before or after major surgery, uncontrolled hypertension, increased risk of bleeding (brain metastases, hemoptysis), nephrotic syndrome, high risk of arterial thromboembolism (after myocardial infarction, stroke).

Dosage of bevacizumab:

10 mg/kg IV every two weeks in combination with interferon alfa-2a 9 MIU SC three times per week (days 2, 4, 6, 9, 11, 13).

Monitoring during therapy:

Regular monitoring of complete blood count with differential, electrolytes including phosphate, liver function tests, blood glucose, coagulation studies, thyroid function tests, serum creatinine, urinalysis for proteinuria, skin and oral mucosa examination, and blood pressure.

Supportive therapy:

Loperamide for diarrhea; antihypertensive therapy for treatment-emergent hypertension; skin care for exanthems; electrolyte replacement as needed; regular mouth rinses for mucositis.

References

Escudier, B., Pluzanska, A., Koralewski, P., Ravaud, A., Bracarda, S., Szczylik, C., Chevreau, C., Filipek, M., Melichar, B., Bajetta, E., Gorbunova, V., Bay, J.O., Bodrogi, I., Jagiello-Gruszfeld, A., & Moore, N. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomized, double-blind phase III trial. Lancet. 2007;370:2103–2111.

Motzer, R.J., & Bukowski, R.M. Targeted therapy for metastatic renal cell carcinoma. J Clin Oncol. 2006;24:5601–5608.

Motzer, R. J. & Bukowski, R. M. Targeted therapy for metastatic renal cell carcinoma.
J Clin Oncol, 2006, 24, 5601-5608.

  Deutsche Version: Bevacizumab

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