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2/13/2004

FDA Approves Erbitux

Kate Traynor

The Food and Drug Administration (FDA) announced yesterday that it has approved the marketing of cetuximab, or Erbitux, for the second-line treatment of advanced metastatic colorectal cancer.

Cetuximab is to be used in combination with irinotecan in patients with irinotecan-refractory metastatic colorectal cancer and as a single agent in patients who cannot tolerate irinotecan therapy. The antibody was developed through a partnership between ImClone Systems and Bristol-Myers Squibb. According to the companies, cetuximab will be available to physicians and pharmacies within two weeks.

Cetuximab is a recombinant monoclonal antibody that blocks the human epidermal growth factor receptor, or HER-1, a transmembrane glycoprotein that is overexpressed in certain cancer cells and is present on the surface of some noncancerous cells. Cetuximab therapy is limited to patients whose cancerous cells express HER-1, which can be detected using a newly-approved diagnostic kit from DakoCytomation.

The FDA-approved labeling for cetuximab contains a boxed warning regarding severe and occasionally fatal infusion-related reactions that have occurred among patients treated with the product. According to the warning, 90 percent of severe reactions occurred during the first treatment. Severe reactions involved rapid-onset airway obstruction, hives, and hypotension.

The labeling instructs health care providers to closely monitor patients for infusion-related reactions and to immediately and permanently halt treatment if a severe reaction occurs. Patients with milder reactions may continue therapy using half of the usual recommended dosage.

The recommended starting dosage of cetuximab is an initial dose of 400 mg per square meter of body surface area delivered as a 120-minute intravenous (i.v.) infusion. Thereafter, the recommended dosage is 250 mg per square meter of body surface area delivered as a weekly 60-minute i.v. infusion. The maximum infusion rate for any dose is 5 mL/min. According to the labeling, cetuximab can be delivered using an infusion pump or a syringe pump.

Before each infusion of cetuximab, patients should receive a dose of a histamine H1-receptor antagonist, such as 50 mg of diphenhydramine hydrochloride by i.v. injection. The labeling advises that "medical resources" should be available during cetuximab infusions to treat any severe infusion-related reaction that occurs.

In clinical trials, about 90 percent of patients reported the development of an acne-like rash during cetuximab therapy. The product's labeling suggests adjusting the dosage of cetuximab if the acne-like rash is severe. Other common adverse events included weakness, diarrhea, nausea and vomiting, abdominal pain, fever, and constipation. Rare but serious adverse events included sepsis, kidney failure, pulmonary embolus, and dehydration.

Cetuximab will be supplied as a 50-mL single-use vial containing 100 mg of the drug at a concentration of 2 mg/mL in phosphate-buffered Water for Injection, USP, with sodium chloride. A small amount of white particulate cetuximab may be visible in the solution, which is otherwise clear and colorless.

Cetuximab, as supplied by the manufacturer, requires refrigeration but should not be frozen. When prepared in an infusion container, the product is stable for up to 12 hours under refrigeration and up to 8 hours at controlled room temperature.