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A Clinician’s Perspective on ASCO 2001: Going After the Epidermal Growth Factor Receptor

A Clinician’s Perspective on ASCO 2001: Going After the Epidermal Growth Factor Receptor

Among the most exciting new anticancer products presented at the 2001
ASCO meeting were new drugs that block the epidermal growth factor receptor
(EGFR). About 30% to 90% of carcinomas express high levels of EGFR. These
include, among others, head and neck cancer, lung cancer, pancreatic cancer,
colon cancer, breast cancer, ovarian cancer, and bladder cancer.

New smart antibodies and small molecules target these receptors and
trigger intracellular mechanisms that block their function. The function of
EGFR is to activate a pathway leading to uncontrolled tumor growth.
Preclinical studies indicate that blocking this pathway can result in cancer
cell death as well as potentiation of the anticancer effects of chemotherapy
and/or irradiation.

So What Are These Antibodies and Smart Molecules?

Monoclonal Antibodies

First, and further along in the clinical testing arena, is C225 (cetuximab,
made by Imclone), a monoclonal antibody that binds to extracellular EGFR. In
abstract #7 of the 2001 ASCO Proceedings, Dr. Leonard Saltz from Memorial
Sloan-Kettering Cancer Center working with Cancer Care Associates in
Florida, the group at New York University, and our Pacific Shores Medical
Group in Long Beach, as well as others, presented results on cetuximab plus
irinotecan (Camptosar) in patients with progressive, refractory, colorectal

We treated 120 patients with metastatic colorectal cancer, refractory to
previous chemotherapy with both fluorouracil (5-FU) and leucovorin as well
as irinotecan, whose tumors tested positive for EGFR. Importantly, 72% of
the tumors tested were positive for EGFR.

Complete and partial responses were seen in 22.5% of patients with a
median duration of 6 months, and an additional 9% of patients had
stabilization of disease. (The results were important because patients not
expected to respond to any therapy achieved significant and durable control
of their cancers.) Based on these encouraging results in refractory
patients, a front- line chemotherapy program in combination with cetuximab
in advanced and previously untreated colorectal cancer is planned.


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