Jane S. Ricciuti, RPh, MS


April 05, 2004

In This Article

Anticancer Agents

(cetuximab) Injection

Manufacturer: ImClone

Drug Approval Classification: Biologic License Application (Approval Date: 02/12/04)

Indication: Erbitux (cetuximab), used in combination with irinotecan, is indicated for the treatment of epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy.

Cetuximab administered as a single agent is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma in patients who are intolerant to irinotecan-based chemotherapy.

The effectiveness of cetuximab is based on objective response rates. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with cetuximab.

Dosing: The recommended dose of cetuximab, in combination with irinotecan or as monotherapy, is 400 mg/m2 as an initial loading dose (first infusion), administered as a 120-minute intravenous infusion (maximum infusion rate, 5 mL/min). The recommended weekly maintenance dose (all other infusions) is 250 mg/m2 infused over 60 minutes (maximum infusion rate, 5 mL/min).

Clinical Summary: Cetuximab is a monoclonal antibody that targets EGFR-expressing cancer cells. Cetuximab was studied in 2 randomized controlled clinical trials in combination with irinotecan in 329 patients and 138 patients. The combination treatment of cetuximab and irinotecan shrank tumors in 22.9% of patients and delayed tumor growth by approximately 4.1 months.

Cetuximab was studied as a single agent in a multicenter, open-label, single-arm clinical trial in patients with EGFR-expressing metastatic colorectal cancer who progressed following an irinotecan-containing regimen. The overall response rate was 9% for the all-treated group and 14% for the irinotecan-failure group. The median times to progression were 1.4 and 1.3 months, respectively. The median duration of response was 4.2 months for both groups.

Two studies involving approximately 2000 patients are currently under way to assess the clinical benefits of cetuximab. These studies are specifically examining the ability of cetuximab to stop the progression of colorectal cancer and to extend the amount of time patients survive with the disease.

Adverse Effects: The most serious adverse reactions experienced during clinical trials included infusion reaction (3%), dermatologic toxicity (1%), interstitial lung disease (0.5%), fever (5%), sepsis (3%), kidney failure (2%), pulmonary embolism (1%), dehydration (5%), and diarrhea (6%).

Pharmacokinetics: Cetuximab exhibits nonlinear pharmacokinetics. The AUC increased in a dose-proportional manner as the dose increased from 20 to 400 mg/m2. The mean elimination half-life was 97 hours (range, 41-213 hours). Cetuximab reached steady-state levels by the third weekly infusion. The mean half-life was 114 hours (range, 75-188 hours).

Erbitux (cetuximab) Injection Labeling