Boosting Colon Cancer Survival

By Jeffrey Norris

Colon cancer is largely preventable and curable when detected early through routine screening. But patients who skip screening or who fall prey to particularly aggressive colon cancers may already have widespread disease by the time they are diagnosed. Colon cancer that has spread to other organs, called metastatic colon cancer, historically has almost always been fatal. For this reason, colon cancer remains the second leading cause of US cancer death, after lung cancer. But now new drugs, often combined with older chemotherapies, in some cases are shrinking widespread cancers to a degree that makes surgery an option and complete elimination of these cancers a possibility. Among metastatic colon cancers, those in which metastasis beyond the colon shrinks to a single, surgically removable mass in the liver often have the best prognosis. Two of the newest targeted treatments approved for colon cancer are being combined with standard chemotherapy in a new, nationwide clinical trial. While chemotherapies tend to target all rapidly dividing cells, the new treatments - called biologics - more specifically target biochemical pathways that are abnormal in cancer cells. UCSF Oncologist Leads National Study UCSF chief of gastrointestinal oncology Alan Venook leads the new clinical trial, called CALGB 80405. The trial is sponsored by the National Cancer Institute through its Clinical Trials Cooperative Groups Program. A consortium of oncologists at academic medical centers, as well as community oncologists, will enroll 2,278 patients in the study. The new treatment combinations will be evaluated to determine whether any of the combinations improve survival of patients with metastatic colon cancer beyond the current average of 22 months. Researchers will measure cures, overall average survival time and how long cancers are prevented from spreading again.

Alan Venook

"Here's a study of advanced colon cancer in which we're wondering what percentage of patients we can cure, whereas 10 years ago, we would not have expected to cure any of these patients," Venook says. "It's an area of great excitement." Novel chemotherapy combinations first boosted survival in cases of widespread colon cancer to about one in 10, Venook says. And still more recent clinical trials suggest that the addition of one biologic drug to chemotherapy may double survival to two in 10 patients. Researchers suspect that, as the new drug combinations course through the body, they are not only shrinking detectable colonies of cancerous cells, but also killing far-flung, unseen cancerous cells that otherwise would seed new tumor growth. Patients who are participating in CALGB 80405 all have been diagnosed with metastatic colon cancer and have not been treated outside the trial. Patients take one of two standard chemotherapy treatments that combine 5-fluorouracil and leucovorin with either oxaliplatin or irinotecan. In addition to receiving a choice of chemotherapy, patients are being randomly assigned to receive one or two biologic drugs - Erbitux, Avastin or both. First Combination of Biologics CALGB 80405 is the only large-scale US clinical trial in which Avastin and Erbitux are being combined as part of first-line therapy for metastatic colon cancer. Erbitux is an engineered antibody similar to those produced by the immune system to specifically target agents of disease. Erbitux targets a molecule called epidermal growth factor receptor (EGFR). EGFR is abnormally abundant in many colon cancers. Based on review of previous clinical trial results, Erbitux is approved by the US Food and Drug Administration as a treatment in metastatic colon cancer in combination with irinotecan, or for patients who cannot tolerate irinotecan. Avastin is another antibody. It targets a circulating protein called vascular endothelial growth factor, which can signal cancer cells to grow and create a blood supply. Avastin is approved for the treatment of metastatic colon cancer in combination with 5-fluorouracil. As part of CALGB 80405, researchers will analyze patient information and biological samples - blood and tumor specimens - that may yield valuable information on patient and tumor characteristics to help predict responsiveness to new drug regimens. Findings from basic research on these biological samples also may lead to new ideas for treatment. This story originally appeared in Cancer Center Report, volume 9.1, Winter 2007. Virtual colonoscopy image/Judy Yee Related Links: Colon Cancer Screening Can Save Your Life (PDF) Cancer Center Report, Volume 8.1, page 6, Spring 2006 UCSF Comprehensive Cancer Center