A novel biologic agent, SU5416, has shown promising activity for the treatment of advanced colorectal cancer, according to results presented at the 37th Annual Meeting of the American Society of Clinical Oncology.
Cancer of the colon and rectum is the second leading cause of cancer related deaths in the United States. Advanced colorectal cancer means that cancer has spread from its site of origin to distant places in the body, often invading vital organs. Recently, a new standard of care has emerged for advanced colorectal cancer, consisting of the chemotherapy combination Camptosar®, 5-Fluorouracil (5-FU) and Leucovorin (LV). Despite progress being made in the treatment of this disease, overall long-term survival for this group of patients is suboptimal following standard therapy. Therefore, researchers have been evaluating novel strategies for treatment of advanced colorectal cancer.
A new arena of cancer research involves the inhibition of angiogenesis. Cancer cells require food, oxygen and growth proteins in order to grow and spread. These essential nutrients are transported to the cancer cells by blood vessels. Angiogenesis is the process of creating new blood vessels necessary to transport “food” to the cancer cells. Two key proteins that are necessary for the process of angiogenesis are called matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF). VEGF causes endothelial cells (cells comprising the innermost layer of blood vessels) to replicate and migrate from existing blood vessels to the cancer. Endothelial cells secrete MMPs, which create an opening in existing tissues surrounding the cancer, allowing the endothelial cells to move near the cancer and form new blood vessels to “feed” the cancer.
SU5416 is a novel angiogenesis inhibitor still being evaluated in clinical trials. SU5416 produces its anti-angiogenic effects by binding to VEGF receptors on cancer cells, which inhibits the action of VEGF. This halts the growth of new blood vessels necessary to promote cancer cell growth.
Recently, researchers from UCLA conducted an early phase clinical trial to evaluate SU5416 in the treatment of advanced colorectal cancer. Patients received treatment consisting of SU5416 plus 5-FU/LV. Outcomes from similar patients receiving this regimen were compared with outcomes of patients treated with either
Camptosar®/5-FU/LV or 5-FU/LV. The time to cancer progression following treatment was 9 months for patients who had received SU5416/5-FU/LV, 9.3 months for patients who had received Camptosar®/5-FU/LV and 5.5 months for patients who had received 5-FU/LV.
The estimated average survival following treatment was 22.6 months for patients who had received SU5416/5-FU/LV compared with an average survival of 26.4 months for patients who had received
Camptosar®/5-FU/LV and 16.2 months for patients who had received 5-FU/LV. It is important to note, however, that a disproportionately high percentage of patients receiving SU5416 in this trial had failed prior therapy with 5-FU/LV compared with the other two reference groups of patients. This fact alone may have biased outcomes in the SU5416 group.
These results suggest that SU5416 in combination with chemotherapy may have potential benefit in the treatment of advanced colorectal cancer. A clinical trial is currently underway evaluating the combination of SU5416 and
Camptosar® for the treatment of advanced colorectal cancer. Patients with advanced colorectal cancer may wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating SU5416. Two sources of ongoing information about clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute (cancer.gov) and eCancerTrials.com. eCancerTrials.com also provides personalized clinical trial searches on behalf of patients. (Proceedings from the 37th Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, Abstract 571, May 2001)