Bevacizumab in combination chemotherapy for colorectal and other cancers.

PURPOSE: The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effects, and dosage and administration of bevacizumab in patients with colorectal and other cancers are reviewed.
SUMMARY: Bevacizumab is a recombinant human monoclonal antibody that inhibits the biological activities of vascular endothelial growth factor (VEGF), a protein involved in the neovascularization of multiple malignant tumors. A single dose of bevacizumab 0.1-10 mg/kg yields a maximum concentration of 2.8-284 microg/mL and shows a dose-response relationship. Pre-clinical and clinical studies have shown that bevacizumab has both cytostatic and cytotoxic effects, resulting in a reduction in tumor growth and increases in median survival time and time to tumor progression. Bevacizumab is available as an intravenous agent and carries FDA-approved labeling for use in the first-line treatment of meta-static colorectal cancer in combination with fluorouracil-based chemotherapy. Bevacizumab 5 mg/kg is infused intravenously over 30-90 minutes every two weeks. No dosage reductions are required for patients with renal or hepatic dysfunction. Bevacizumab has also yielded preliminary evidence of efficacy for breast, non-small-cell lung, pancreatic, prostate, renal, and hepatic cancers, as well as for melanoma and acute myelogenous leukemia. The most frequent adverse effects are nausea, vomiting, headache, epistaxis, anorexia, stomatitis, dyspnea, and constipation.
CONCLUSION: Bevacizumab combined with fluorouracil-based chemotherapy has become the standard of care for the first-line treatment of metastatic colorectal cancer and may prove useful for other tumors as well.