First Angiogenesis Inhibitor for Colorectal Cancer

The U.S. Food and Drug Administration (FDA) has approved bevacizumab (Avastin™, Genentech) as a first-line treatment for patients with metastatic colorectal cancer. A monoclonal antibody, it is the first FDA-approved product that prevents the formation of new blood vessels, a process known as angiogene-sis. Avastin™ extended patients’ lives by about five months when it was given intravenously as a combination treatment with standard chemotherapy drugs for colon cancer in a regimen consisting of ironotecan, 5-fluorouracil (5-FU), and leucovorin (IFL).

Avastin™ is a genetically engineered version of a mouse antibody that contains both human and mouse components. Special technology allows it to be produced in large quantities in the laboratory.

This product targets and inhibits a natural protein, called vascular endothelial growth factor (VEGF), which stimulates new blood vessel formation. When VEGF is bound to Avastin™, tumors are denied blood, oxygen, and other nutrients needed for their growth.

Colorectal cancer is the third most common cancer affecting men and women in the U.S. and the second leading cause of cancer-related deaths.

A clinical trial of more than 800 patients with metastatic colorectal cancer was designed to determine whether Avastin™ extended the lives of patients. Roughly half the patients received IFL, the standard chemotherapy combination, and the other half received Avastin™ once every two weeks in addition to IFL. Overall, patients given Avastin™ with IFL survived about five months longer, and the average time before tumors started regrowing or new tumors appeared was four months longer than patients receiving IFL alone. The overall response rates were 45% for the treated patients and 35% for the controls.

Serious but uncommon side effects include gastrointestinal perforation, impaired wound healing, and pulmonary or internal bleeding. Other more common effects are hypertension, fatigue, blood clots, diarrhea, decreased white blood cells, headache, appetite loss, and mouth sores.