In a Phase II trial, treatment with a monoclonal antibody that inhibits the activity of epithelial growth factor receptor has been shown to shrink colorectal tumors in patients refractory to standard chemotherapy. Results from the trial reported by Dr. Leonard Saltz, which show activity of the antibody cetuximab (IMC-C225), are of particular interest because patients with colorectal cancers that do not respond to 5-fluoruracil and irinotecan currently have no other therapeutic options.

Cetuximab (IMC-C225) also represents one of the first clinical successes of therapy designed to act at a specific molecular target in cancer cells. The antibody binds to the epithelial growth factor receptor to block intracellular growth signals.

The Phase II trial included 120 patients who had epithelial growth factor receptor-positive metastatic colorectal cancers that had progressed during treatment with irinotecan. When cetuximab was administered with the same dose of irinotecan, 22.5% of patients had reduction of tumor by 50% or more. An additional 7.5% achieved stable disease.

Few side effects specific to cetuximab were noted except for an acne-like rash that occurred in the majority (61%) of patients. The rash was not dose-limiting.

Dr. Saltz noted that it cannot be determined from the current nonrandomized study if use of cetuximab will result in increased survival. However, the 22.5% response rate with cetuximab compares well with the 13% response rate for irinotecan in tumors resistant to 5-fluorouracil, the only other example of successful treatment of refractory colorectal tumors.

To qualify for treatment with cetuximab, patients had to have tumors demonstrated to have epithelial growth factor receptors. The researchers found that 72% of 400 patients with refractory colorectal cancer who were screened for the trial had epithelial growth factor receptor-positive tumors, a higher percentage than was expected.

Dr. Saltz stated that the results with colorectal cancer have stimulated interest in treating other epithelial growth factor receptor-positive cancers with cetuximab. A trial for lung cancer is underway and there are plans for trials for pancreatic as well as head and neck cancers.

An application for fast-track licensing of the drug is expected to be filed with the U.S. Food and Drug administration in June 2001.