NEW YORK CITYPromising early data are emerging from a phase II colon cancer trial of irinotecan(Drug information on irinotecan) (Camptosar) plus cetuximab(Drug information on cetuximab) (IMC-C225), a chimeric monoclonal antibody that targets the epidermal growth factor receptor (EGFR), reported Leonard Saltz, MD. He is associate attending physician on the Gastrointestinal Oncology Service at Memorial Sloan-Kettering Cancer Center in New York City.
EGFR is emerging as an important area of colon cancer research because preventing activation of this receptor prevents transduction of signals that favor cell growth and survival. Current attempts to block EGFR function include monoclonal antibodies and tyrosine kinase inhibitors (both of which block signal transduction), toxin conjugates (which cause cell death after they are internalized), and antisense molecules (which interfere with protein synthesis).
Cetuximab blocks the binding of growth factor to the receptor and prevents tyrosine kinase-mediated cell signaling. The rationale for combining cetuximab with irinotecan was preclinical evidence of synergy between the two compounds. "There was also a striking response in irinotecan-refractory patients that received cetuximab plus irinotecan on a compassionate release protocol," Dr. Saltz said.
Dr. Saltz updated data from a phase II irinotecan/cetuximab study he presented earlier this year at the American Society of Clinical Oncology annual meeting. The trial included 120 patients with documented progressive disease on irinotecan and a parallel group of 18 patients who had stable disease on irinotecan. Dr. Saltz said the stable-disease group was included in the protocol "to keep the study group pure for irinotecan resistance."
All patients had measurable metastatic colorectal cancer and EGFR expression on tumor samples documented by immunohistochemistry. Patients had no intercurrent chemotherapy between irinotecan failure and protocol entry.
Patients were treated with cetuximab plus the same dose and schedule of irinotecan on which they had previously progressed. Patients were premedicated with diphenhydramine(Drug information on diphenhydramine), and cetuximab was given as a 20 mg test dose on day 1, followed by a 400 mg/m² loading dose and then biweekly doses of 250 mg/m².