ImClone Systems Incorporated and Bristol-Myers Squibb announced data from studies suggesting that the investigational monoclonal antibody, Erbitux (cetuximab), had anti-Tumour activity as a single-agent in chemotherapy-resistant colorectal cancer -- and in combination with the standard chemotherapy agents irinotecan, fluorouracil (5-FU) and leucovorin -- in patients with previously untreated colorectal cancer.

The data from the single-agent study and the combination therapy study were presented by Leonard Saltz, M.D., Associate Attending Physician, Memorial Sloan-Kettering Cancer Center, and Arthur H. Rosenberg, M.D., F.A.C.P., Medical Director, Bendheim Cancer Center at Greenwich Hospital, respectively.

In the 57-patient phase II trial that evaluated cetuximab as a single-agent treatment for refractory colorectal cancer, six patients (10.5 percent) achieved a partial response (characterized as greater than 50 percent Tumour regression) and an additional 21 (36.8 percent) had achieved stabilization of disease. The overall rate of disease control (partial response plus stable disease) is 47 percent. The patients in the single-agent trial had failed prior treatment with fluorouracil, leucovorin and irinotecan, and had tested positive for EGFR using an immunohistochemistry test.

The most common adverse events reported during the single-agent study using cetuximab were an acne-like skin rash (occurring in 86 percent of patients) and asthenia (occurring in 54 percent of patients).

"This study provides important information about the single-agent activity of cetuximab in patients with refractory colorectal cancer," said Dr. Saltz.

The combination regimen study (abstract #536) evaluated the use of cetuximab in combination with a chemotherapy regimen consisting of irinotecan, fluorouracil and leucovorin in 29 patients with previously untreated EGFR-positive metastatic colorectal cancer. Of the 29 patients in the study, 14 patients (48.3 percent) achieved a partial response (characterized as greater than 50 percent Tumour regression), 9 patients (31 percent) achieved a minor response (characterized as less than 50 percent Tumour regression) and 3 patients (10.3 percent) achieved stable disease. The overall rate of disease response (partial response plus stable disease) is 89.6 percent.

The most common adverse events reported during the study using the combination of cetuximab and irinotecan, fluorouracil and leucovorin were neutropenia (occurring in 59 percent of patients), an acne-like rash (occurring in 76 percent of patients), nausea (occurring in 69 percent of patients), diarrhea (occurring in 69 percent of patients), and mucositis (occurring in 59 percent of patients).

"These data using cetuximab with the three-drug chemotherapy regimen suggest this combination can be safely administered with first-line chemotherapy to patients with newly-diagnosed colon cancer," said Dr. Rosenberg. "Randomized studies will be necessary to determine if combining cetuximab with first line chemotherapy will lead to improved treatments for advanced colorectal cancer."

Cetuximab, also known as C225, is an investigational drug designed to target and block the Epidermal Growth Factor Receptor (EGFR), which according to previous research, is expressed in many solid Tumours including colorectal carcinoma. Cetuximab is being co-developed by ImClone Systems Incorporated and Bristol-Myers Squibb in the United States and Canada. The companies also maintain co-development rights in Japan.

According to the American Cancer Society, in 2001 there were about 135,000 cases of colorectal cancer diagnosed and over 56,000 deaths attributed to this type of cancer. Colon cancer is the second leading cause of cancer deaths, second only to lung cancer.

ImClone Systems Incorporated and Bristol-Myers Squibb are studying cetuximab in a series of Phase II and Phase III clinical trials. The companies are conducting Phase II clinical studies of cetuximab in combination with standard therapies in patients with various stages of colorectal cancer, pancreatic cancer, head and neck cancer, and non-small cell lung cancer. In addition to the Phase II studies, the companies are planning Phase III clinical trials in a number of Tumour types where EGFR is expressed. The most common drug-related adverse events reported in clinical trials of cetuximab has been an acne-like rash. Severe allergic reactions may occur in a small percentage of patients.