mono-clonal antibody cetuximab (Erbitux, also known as C225, ImClone Systems)
has modest single-agent activity in irinotecan (Camptosar)-refractory
colorectal cancer expressing epidermal growth factor receptor (EGFR),
researchers said at the American Society of Clinical Oncology 38th Annual
Meeting (abstract 504).
The most significant toxicities of cetuximab, which
selectively binds to EGFR, are allergic reactions and an acne-like rash, said
Leonard Saltz, MD, of Memorial Sloan-Kettering Cancer Center. "As would be
expected from a monoclonal antibody, the typical cytotoxic toxicities [ie,
hematologic, gastrointestinal] are virtually absent," he said.
One year earlier at ASCO, Dr. Saltz reported that cetuximab
was effective in combination with irinotecan in patients with EGFR-positive
disease who had already failed prior irinotecan therapy, with a response rate
of 22%. This year, he reported a response rate of 10% for cetuximab monotherapy
in that setting.
"C225 is active both as a single agent and in combination
with CPT-11 [irino-tecan]," Dr. Saltz said. "Further studies will be needed to
define optimal strategies for use of this agent."
According to David Cunningham, MD, of the Royal Marsden MHS
Trust, London and Surrey, UK, the present study demonstrates "important
activity" for cetuximab monotherapy in colorectal cancer resistant to
chemotherapy. "The response rate may be lower than when combined with
irinotecan," Dr. Cun-ningham said. "However, single-agent cetuximab is well
tolerated and may be suitable for a wider range of patients."
Investigators evaluated cetuximab/irinotecan first because
in prior preclinical studies, the combination produced tumor regression in
colon cancer xenografts, while cetuximab alone appeared less active than the
combination (albeit more active than saline control).
"So, it’s perfectly appropriate that we undertook the most
interesting combination first," Dr. Saltz said. "But now we need to look at
what can happen with cetuximab alone."