Future directions in the use of antiangiogenic agents in patients with colorectal cancer.
Considerable progress has been achieved in the treatment of colorectal cancer over the last few years, but it remains a major cause of cancer death in the United States. Among the most important recent developments is the understanding that angiogenesis is a fundamental requirement of early tumor growth and metastasis and therefore is an important target for therapy. The recent positive results obtained by adding bevacizumab to a standard regimen of chemotherapy highlight the potential impact of angiogenesis. Although not the final answer to the problem of advanced colorectal cancer, the success obtained with bevacizumab should encourage the development of even more effective and less toxic molecular targeted agents and regimens. The tyrosine kinase inhibitor vatalanib (PTK787/ZK222584) is in the final stages of clinical development, and several other promising compounds will be available for clinical development in the near future. Agents already commercially available, such as the monoclonal antibody cetuximab, may have some antiangiogenic properties as well. However, the greatest benefit from antiangiogenic therapies may come from their combined use, not only with conventional chemotherapy but also with other molecular targeted agents, radiotherapy, and surgery in a true multidisciplinary approach.