New Targeted Therapy for Treatment of Resistant Colorectal Cancer

The drug cetuximab, a promising new targeted therapy better known as Erbitux, offers another option for patients who have colorectal cancer that resists standard chemotherapy treatment, according to an editorial written by two Mayo Clinic cancer researchers that will be published in the July 22 edition of the New England Journal of Medicine (NEJM).

The editorial is co-authored by Mayo Clinic’s Charles Erlichman, M.D., chair of the Department of Oncology and a specialist in the research and treatment of colorectal cancer, and Daniel Sargent, Ph.D., director of Cancer Center Statistics.

The editorial comments on a phase 2 randomized, three-year study that compared cetuximab combined with irinotecan, a standard chemotherapy regimen, to cetuximab alone in patients with metastatic colorectal cancer that is resistant to treatment with irinotecan. The study was led by David Cunningham, M.D., Royal Marsden Hospital, London and Surrey, in the United Kingdom, and its results will be published in the same issue of NEJM.

Dr. Erlichman notes that although the study indicated the benefits of cetuximab were modest in terms of stopping the cancer, patients’ response to the drug, and survival, it is nonetheless a step forward in the treatment of colorectal cancer that has spread to other parts of the body.

“Cetuximab combined with irinotecan offers patients with metastatic colorectal cancer another treatment option after failing treatment with irinotecan,” he says.

About 150,000 people in the U.S. will be diagnosed with colorectal cancer this year, and more than 57,000 will die from it. Colorectal cancer is the second most common cancer in this country, accounting for about 10 percent of annual cancer deaths.

Irinotecan is a chemotherapy drug that is used alone or combined with two other chemotherapy drugs, fluorouracil and leucovorin, for treatment of patients with colorectal cancer. Oxaliplatin is another approved chemotherapy regimen that can be used in combination with fluorouracil and leucovorin as first-line treatment for colorectal cancer, or in patients who have failed irinotecan.

Cetuximab belongs to a new class of cancer drugs called targeted therapies, so named because the drugs go after the source of the cancer and leave healthy cells alone. Cetuximab’s purpose is to disable the epidermal growth factor receptor (EGFR), and thereby prevent cancer cell growth and decrease the ability of cancer cells to overcome the killing effect of chemotherapy.

In laboratory studies, cetuximab had been shown to enhance irinotecan’s antitumor abilities. The study to be reported in NEJM intended to determine whether adding cetuximab to irinotecan can resensitize tumors that are resistant to irinotecan. It found that cetuximab can decrease resistance to irinotecan.

However, Dr. Erlichman notes, there was insufficient evidence to prove that cetuximab improved patients’ survival. Additionally, he disagrees with the study author’s claim that cetuximab compares favorably to oxaliplatin therapy in patients whose colorectal cancer is resistant to irinotecan. He says the effectiveness of oxaliplatin therapy has been established in a large randomized phase 3 clinical study, while cetuximab has not been subjected to such validation.

He describes the results of this study as “the first step in defining the role of EGFR antibody targeted therapy in patients with colorectal cancer.”