Jane S. Ricciuti, RPh, MS


April 05, 2004

In This Article

Anticancer Agents

(bevacizumab) Injection

Manufacturer: Genentech

Drug Approval Classification: Biologic License Application (Approval Date: 2/26/04)

Indication: Avastin (bevacizumab) injection, used in combination with intravenous (IV) 5- fluorouracil (5-FU)–based chemotherapy, is indicated for first-line treatment of patients with metastatic carcinoma of the colon or rectum.

Dosing: The recommended dose of bevacizumab is 5 mg/kg given once every 14 days as an IV infusion until disease progression is detected. Bevacizumab therapy should not be initiated for at least 28 days following major surgery. The surgical incision should be fully healed prior to initiation of bevacizumab.

Clinical Summary: Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that binds to and inhibits the biological activity of human vascular endothelial growth factor (VEGF) in both in vitro and in vivo assay systems.

Bevacizumab binds to VEGF and prevents the interaction of VEGF with its receptors on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new blood vessel formation in in vitro models of angiogenesis.

Bevacizumab was evaluated in 2 randomized controlled clinical trials in combination with intravenous 5-FU and an irinotecan-based regimen. Bevacizumab was studied as a single-agent treatment, but the study arm was closed early due to inferior efficacy to combination therapy.

Overall, patients who received bevacizumab once every 2 weeks in combination with 5-FU and irinotecan survived 5 months longer and demonstrated a delay of tumor regrowth by 4 months. The overall response rate to the treatment was 45% vs 35% for the control arm of the trial.

Adverse Effects: Serious but uncommon side effects of bevacizumab include formation of holes in the colon (gastrointestinal perforation) generally requiring surgery and sometimes leading to intra-abdominal infections, impaired wound healing, and bleeding from the lungs or internally. Other, more common side effects are high blood pressure, tiredness, blood clots, diarrhea, decreased white blood cell count, headache, appetite loss, and mouth sores.

Pharmacokinetics: The estimated half-life of bevacizumab is approximately 20 days (range, 11-50 days). The predicted time to reach steady state was 100 days.

The clearance of bevacizumab varies by body weight, gender, and tumor burden. After correcting for body weight, males had a higher bevacizumab clearance (0.262 L/day vs 0.207 L/day) and a larger Vc (3.25 L vs. 2.66 L) than females.

Avastin (bevacizumab) Injection Labeling