Fall 2003 Newsletter: Advances in Treatment of Colorectal Cancer

Richard L. Schilsky, M.D.
Professor, Hematology/Oncology Section, Department of Medicine
Associate Dean for Clinical Research,
Division of Biological Sciences
University of Chicago Medical Center
Chairman, Cancer and Leukemia Group B
Medical Consultant, Cancer Research Foundation

Significant advances in the treatment of colorectal cancer, announced in just the past few months, hold great promise to improve the survival of patients with this common malignancy. Each year approximately 150,000 Americans are diagnosed with colon and rectal cancer and 57,000 individuals die from this disease. Overall, colorectal cancer is the 3rd most common cancer diagnosed in the U.S. and the 3rd most common cause of cancer death in both men and women. Recent advances in early diagnosis, screening and treatment hold great promise for improving the survival of patients with colorectal cancer. In the area of early diagnosis, new molecular diagnostic tests that can detect colorectal cancer at its earliest stages are in development and may eventually enable physicians to detect the disease when only a few malignant cells have developed in the colon and long before bleeding or other symptoms occur.

Although screening for colorectal cancer has been proven to save lives, many people ignore screening recommendations because of concerns about the discomfort of colonoscopy or other invasive tests necessary to examine the full length of the colon. Virtual colonoscopy now provides an option for screening that is less invasive and may, therefore, be more appealing to individuals, particularly those at low risk of having colon polyps or cancer. Virtual colonoscopy is a CT scan examination of the colon that uses sophisticated computer software to reconstruct a three dimensional image of the interior of the colon and allows radiologists to identify polyps or tumors with a high degree of accuracy. Conventional colonoscopy is still necessary if abnormalities are identified but virtual colonoscopy provides an alternative to the more invasive test as an initial screening examination. The technology for virtual colonoscopy has been developed, in part, by University of Chicago radiologists and the test is available at the medical center.

Perhaps the most exciting information about colorectal cancer has come from several recently reported randomized clinical trials that have clearly demonstrated the value of new therapeutic approaches to this disease. A new chemotherapy drug, oxaliplatin (Eloxatin), used in combination with standard chemotherapy (5-FU and leucovorin) has now been shown to provide superior survival for patients with colorectal cancer that has spread throughout the body. In such cases, the FOLFOX chemotherapy program extends median survival into the range of 18-20 months compared to 14-15 months which was the best that could be achieved until now with other chemotherapy programs. The FOLFOX regimen has also been tested as postoperative adjuvant chemotherapy for patientswith high risk, non- metastatic, colon cancer and has been shown to further reduce the likelihood of tumor recurrence after surgery compared with the prior standard regimen.

In another exciting recent development, study results have shown that adding bevacizumab (Avastin) to chemotherapy significantly improves the survival of patients with metatstaic colorectal cancer. Bevacizumab is a monoclonal antibody directed against the vascular endothelial growth factor (VEGF). VEGF is a molecule produced by tumor cells that stimulates the growth of blood vessels to bring nutrients to the tumor tissue. Blockade of the angiogenic signal by bevacizumab has the potential to cut off the blood supply to tumor cells resulting in tumor shrinkage or slower growth. At the 2003 annual meeting of the American Society of Clinical Oncology held in Chicago, Genentech investigators reported results of a randomized clinical trial showing that adding bevacizumab to chemotherapy improved the median survival of patients with metastatic colorectal cancer by approximately 5 months. This is the first study to clearly demonstrate a benefit from any antiangiogenic strategy and validates this approach as an important new component of cancer treatment. Although bevacizumab is not yet commercially available, it is widely anticipated that the drug will receive marketing approval from FDA in the coming year.

When I first became involved in oncology, 25 years ago, the only drug available for treating colorectal cancer was 5-FU. The average survival of patients with metastatic disease was on the order of 8-10 months. Although it has taken a quarter of a century, the outlook for patients with colorectal cancer is now considerably brighter. Three chemotherapy drugs (5-FU, irinotecan and oxaliplatin) are now commercially available and effective for treating this disease and bevacizumab is another very promising molecule that adds a targeted, antiangiogenic approach to our armamentarium of agents for use in treating colorectal cancer. The median survival of patients with metastatic disease has doubled from 8-10 months in the 1970s to 20 months or better at the present time. The use of adjuvant chemotherapy in the postoperative setting continues to improve outcomes for patients with early stage disease as well. New tools for molecular diagnosis of early stage disease and new technology for early detection of colon cancer, if widely used, will enable detection of the disease at an earlier, even more treatable stage. For patients with colon polyps who are at increased risk of developing colon cancer, recent studies conducted by the Cancer and Leukemia Group B and other groups, suggest that daily aspirin therapy is effective in reducing the number and size of polyps and may therefore be effective in reducing the development of colorectal cancer as well. Other anti-inflammatory drugs, such as inhibitors of cyclooxygenase II (COX-II), also hold great promise for preventing colon polyps and colon cancer.

Andrew Von Eschenbach, M.D.,Director of the National Cancer Institute, has declared a goal of eradicating the pain and suffering due to cancer by 2015. At least for colorectal cancer, we are already well on our way toward meeting that goal and the future is bright indeed.