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?
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(Drug information on cetuximab) plus irinotecan(Drug information on irinotecan) (Camptosar) in patients with progressive, refractory, colorectal carcinoma.
We treated 120 patients with metastatic colorectal cancer, refractory to previous chemotherapy with both fluorouracil(Drug information on 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.