The Food and Drug Administration (FDA) last week approved the first angiogenesis inhibitor, bevacizumab (Avastin™), to be used in combination with intravenous 5-fluorouracil-based chemotherapy in the first-line treatment of patients with metastatic colorectal cancer. Attempts to develop drugs that prevent angiogenesis - the formation of new blood vessels that can fuel tumor growth - have been under way for more than three decades.

"The approval of Avastin…is one of a number of recent new treatments for colorectal cancer that, taken together, have significantly improved the armamentarium for fighting this disease," said FDA Commissioner Dr. Mark B. McClellan. Recently the FDA also approved cetuximab (Erbitux™) for use in patients with metastatic colorectal cancer that had progressed after treatment with standard irinotecan- based chemotherapy.

Such advances, noted Dr. William Figg, head of the Clinical Pharmacology Research Core in the NCI Center for Cancer Research and co-chair of the NCI Angiogenesis Working Group, are important for the treatment of all cancers. "The approval of bevacizumab has a big impact," he said. "It proves that this pathway, angiogenesis, is important and can be targeted. It also renews interest in drug development of antiangiogenesis agents and moves us beyond proof-of-principle type trials to finding agents or combinations that impact patients."

Bevacizumab is a monoclonal antibody that is thought to work by inhibiting vascular endothelial growth factor, or VEGF, a protein that plays an important role in angiogenesis. In a study presented at the 2003 American Society of Clinical Oncology annual meeting, patients with newly diagnosed metastatic colon cancer who received bevacizumab in combination with a chemotherapy regimen known as IFL (irinotecan, 5-fluorouracil, and leucovorin) survived longer and had longer periods without cancer progression than those in the IFL-alone group. In its approval, the FDA stated bevacizumab can be used in combination with any chemotherapy regimen that includes 5-FU for patients with untreated metastatic colorectal cancer.

In the 1960s, Harvard researcher Dr. Judah Folkman postulated that angiogenesis fueled tumor growth and that therapies could be designed to block this action. NCI has long provided support for Dr. Folkman's research in this area. In addition, NCI's Cancer Therapy Evaluation Program, in collaboration with Genentech, is sponsoring more than 30 trials to investigate the use of bevacizumab in other settings of colorectal cancer and in patients with a variety of solid tumor and hematological malignancies.

NCI, along with other NIH institutes and the Juvenile Diabetes Research Foundation, has established a trans-institute angiogenesis initiative to find overlapping opportunities to apply vascular biology research findings across diseases.

While only one angiogenesis inhibitor has been approved, others may not be far behind. "There are numerous agents in development in both preclinical and clinical settings that look extremely promising," Dr. Figg said.