Related Pages Search for Clinical Trials 1 NCI's PDQ® Cancer Clinical Trials Registry. Colon and Rectal Cancer Home Page 2 NCI's gateway for information about colon and rectal cancer. Highlights from ASCO 2003 3 A collection of links to material summarizing some of the important clinical trial results announced at the 2003 annual meeting of the American Society of Clinical Oncology (ASCO).

Key Words

Colorectal cancer, cetuximab ⁴ ( Erbitux®), irinotecan ⁵ (Camptosar®). (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁶.)

Summary

A randomized phase II trial showed that the combination of cetuximab (Erbitux®) and irinotecan (CPT-11) shrank tumors in more patients and delayed tumor progression longer than cetuximab alone in patients with metastatic colorectal cancer that had progressed after treatment with standard irinotecan-based chemotherapy.

Source

American Society of Clinical Oncology (ASCO) annual meeting, Chicago, June 1, 2003. (The final results were subsequently published in the July 22, 2004, issue of the New England Journal of Medicine; see the journal abstract.)

Background

Previous phase II trials have also suggested that cetuximab is effective against metastatic colorectal cancer and that the cetuximab/irinotecan combination is more effective than cetuximab alone. This large European study offers independent confirmation of these findings.

Cetuximab is a monoclonal antibody under evaluation that targets the epidermal growth factor receptor (EGFR). Two other new agents that work differently, oxaliplatin and bevacizumab (Avastin®), have also recently shown benefit in trials for advanced and metastatic colorectal cancer. New trials are now being planned or are already under way to compare the new agents in various combinations.

The Study

The randomized phase II trial included 329 patients whose colorectal cancer had progressed after treatment with conventional irinotecan-based chemotherapy. Two-thirds of the patients received cetuximab and irinotecan, and one-third received cetuximab alone. Those who received cetuximab alone had the option to switch to the combination treatment if the single agent failed to stem the disease.

The trial was led by David Cunningham, M.D., of Royal Marsden Hospital, Sutton, England.

Results

The combination therapy shrank tumors in 22.9 percent of patients while the single agent was active in just 10.8 percent. Tumor progression was delayed a median of 4.1 months among those who received the two drugs compared to 1.5 months in the group receiving cetuximab alone. Although the survival time was also longer for the combination regimen – 8.6 months compared to 6.9 months – this difference was not statistically significant - that is, it could have occurred by chance.

One-year survival rates were also about 30 percent for both groups, possibly because patients on cetuximab alone were allowed to cross over to the combination therapy when their tumors stopped responding to the single agent.

The results show that the combination of cetuximab and irinotecan “has significant and important activity in patients resistant to chemotherapy,” said Cunningham.

Limitations

This was a phase II study, designed to show that cetuximab was an active agent in this group of patients. Although the patients were randomized to two groups originally, all received cetuximab and those on the single agent were allowed to switch to the combination therapy before the end of the study. A randomized, controlled, phase III trial is needed to confirm the benefits of cetuximab plus irinotecan.

Also, severe side effects were more frequent among patients receiving the combination therapy. About 65 percent had diarrhea, weakness, low white blood cell counts, rash, or vomiting. About 50 percent of patients receiving cetuximab alone had severe side effects, including difficulty in breathing, weakness, and pain.

Glossary Terms

A drug used to treat several types of cancer, including certain types of colorectal, lung, breast, and kidney cancers and glioblastoma. It is also being studied in the treatment of other types of cancer. Bevacizumab binds to vascular endothelial growth factor (VEGF) and may prevent the growth of new blood vessels that tumors need to grow. It is a type of antiangiogenesis agent and a type of monoclonal antibody. Also called Avastin.

Treatment with drugs that kill cancer cells.

A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment.

The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also called EGFR, ErbB1, and HER1.

A statistics term. The middle value in a set of measurements.

A type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.

A drug used together with other drugs to treat colorectal cancer that is advanced or has come back. It is also being studied in the treatment of other types of cancer. Oxaliplatin attaches to DNA in cells and may kill cancer cells. It is a type of platinum compound. Also called Eloxatin.

A study to test whether a new treatment has an anticancer effect (for example, whether it shrinks a tumor or improves blood test results) and whether it works against a certain type of cancer.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are white blood cells. Also called leukocyte and WBC.