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New Treatment Strategies
Antiangiogenic and other “targeted” therapies, including bevacizumab and erlotinib, have become powerful new weapons against advanced colorectal cancer. Combined with standard chemotherapy and radiation, this new generation of drugs promises to both prolong life and improve quality of life for CRC patients. Despite these proven clinical benefits, however, virtually all CRC patients whose cancer has spread (metastasized) to other organs will eventually relapse.

Since most patients with advanced CRC now receive antiangiogenic therapy as part of their initial treatment regimen, an important question is how long to continue this therapy. Should, for example, patients who have had some recurrence or progression of their disease continue to get antiangiogenic therapy?

Considerable evidence shows that antiangiogenic therapy “normalizes” blood flow around the tumor, and enhances the effects of chemotherapy. Research has also shown that tumor blood vessels can regrow aggressively soon after antiangiogenic therapy is halted. Therefore, discontinuing antiangiogenic therapy in the face of tumor growth could initiate even more rapid disease progression. Similarly, continuing therapy beyond progression may provide survival and quality-of-life benefits even in the absence of traditional measures of tumor response, such as shrinkage.

Data from the large observational study of bevacizumab and chemotherapy showed that patients who remained on bevacizumab beyond first progression had significantly prolonged overall survival compared with patients who received no additional bevacizumab or no further treatment at all.5 This may suggest that the cancer progression in these patients may have resulted from chemotherapy resistance rather failure of the antiangiogenic therapy. Further study is required to confirm this hypothesis.

Other strategies being explored in advanced CRC involve the use of drugs that target VEGF and EGFR simultaneously, and drugs that target multiple receptors involved in angiogenesis and tumor growth. In one study, adding the angiogenesis inhibitor bevacizumab to the EGFR inhibitor cetuximab prolonged the time until patients’ cancer progressed by about 5.5 months.6 Other, larger studies are exploring this combination.

Other antiangiogenic drugs include so-called “small molecule” therapies. Unlike antibody therapies that bind to proteins and are administered intravenously, small molecule therapies are taken in pill form and target specific receptors on the surface of cells. Two such agents, vatalanib and sunitinib (Sutent®) have shown some signs of activity in CRC, but larger clinical trials will be required to determine what role, if any, these drugs will have in CRC therapy.


Last updated May 29, 2011