NEW YORK CITYPromising early data are emerging from a phase II colon
cancer trial of irinotecan (Camptosar) plus 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
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, 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.