Study Shows Erbitux May Fight Colorectal Cancer After Other Therapies Fail

"Even in people who have gone through six or more previous courses of chemotherapy, cetuximab, may fight the growth of cancer, giving patients additional months of life," says study presenter Heinz-Josef Lenz, M.D., associate professor of medicine at the Keck School of Medicine of the University of Southern California and USC/Norris Comprehensive Cancer Center.

Lenz and researchers at five other university medical centers in the United States and Europe offered the phase II trial of cetuximab to patients with metastatic colorectal cancer who had already tried and failed treatment with fluoropyrimidine drugs (such as 5-FU) and the drugs irinotecan and oxaliplatin. Some patients had undergone as many as nine prior courses of chemotherapy.

In all, 346 patients participated, and 12 percent of patients saw their tumors shrink, at least temporarily, in response to the drug. The typical patient survived 6.6 months after treatment.

Colorectal cancer is the third most common cancer in the U.S., with nearly 145,300 new cases and nearly 56,300 deaths from the disease expected this year, according to the American Cancer Society. As Lenz explains, the death rate for colorectal cancer has been declining for 15 years because better detection methods are turning up tumors in their early stages, when they can most easily be treated.

The five-year relative survival rate for people whose colorectal cancer is treated in an early stage, before it has spread, is greater than 90 percent. But only 39 percent of colorectal cancers are found at that early stage.

"Unfortunately, treatment for colorectal cancer is much more challenging when the cancer has advanced," says Lenz, a medical oncologist. "That is why we not only need to focus on prevention and early detection, but we also need to work toward more successful treatment options for patients in these advanced stages."

Cetuximab is one of a new breed of cancer-fighters, Lenz explains. It was the first targeted therapy approved by the U.S. Food and Drug Administration for treating colorectal cancer.

As a monoclonal antibody, cetuximab that seeks out and locks to special molecules called epidermal growth factor receptors (EGFR) that may appear in abundance on the surface of a cancer cell. Once the antibody is attached, it blocks substances called epidermal growth factors (EGF) from fitting into the receptors. EGF gives orders for a cancerous cell to grow, so blocking EGF interferes with growth.

Most colorectal cancers express EGFR, and high levels of EGFR are usually associated with more metastases and poor prognosis, Lenz explains.

Cetuximab also prevents DNA from being repaired, blocks metastasis and suppresses the formation of blood vessels to nourish the tumor, he adds.

The most frequently reported side effects were skin rashes, weakness and nausea.

Heinz-Josef Lenz, Robert J. Mayer, Barry Mirtsching, Allen L. Cohn, Andrew W. Pippas, Paul Windt, Cliff Ding and Eric Van Cutsem, "Consistent Response to Treatment with Cetuximab Monotherapy in Patients with Metastatic Colorectal Cancer," 2005 Annual Meeting of the American Society of Clinical Oncology. Gastrointestinal Cancer - General Poster Session, Abstract No. 3536.