Jean L. Grem, MD, FACP

Monoclonal antibodies to the epidermal growth factor receptor (EGFR) are among the promising novel targeted therapies being explored in colorectal cancer. Two such agents that inhibit EGFR signaling by interfering with ligand-binding are cetuximab (Erbitux) and panitumumab (Vectibix). This review will address the use of cetuximab and panitumumab in chemotherapy-refractory colorectal cancer as well as in front-line therapy for the disease, consider predictors of response and resistance, and outline comparisons between these agents.

In this issue, Dr. Saltz articulateshis opinion on a variety of questionsconcerning therapy for patientswith metastatic colorectal cancer.My commentary will reflect myopinions concerning these questions.

Randomized studies have tested a variety of strategies to improve the activity of 5-fluorouracil (5-FU) in colorectal cancer patients. Results from 14 randomized trials comparing 5-FU administered via intravenous ( IV) bolus either

Damjanov and Meropol review the status of several oral fluoropyrimidine drugs that are currently undergoing clinical testing for the treatment of colorectal cancer. Meta-analysis indicates an 8% improvement in the overall response rate and a survival advantage of 0.8 months with infusional vs bolus fluorouracil (5-FU)-arguably small differences. The incidence of grade 3-4 diarrhea, mucositis, and myelosuppression is < 10% with infusional 5-FU, although hand-foot syndrome is commonly associated with this therapy. The prevailing strategy for the development of oral 5-FU drugs employs multiple daily dosing for periods of 2 to 4 weeks followed by a 1- or 2-week break in order to mimic the protracted infusional schedule.UFT