Erbitux

Cetuximab for IV infusion
IMCLONE/BRISTOL-MYERS SQUIBBMonoclonal antibody approved for head and neck cancer

Cetuximab binds specifically to the epidermal growth factor receptor (EGFR), a transmembrane protein expressed in many human cancers, including those of the head and neck, colon, and rectum. An additional indication was approved for cetuximab on March 1, 2006, to include use in combination with radiation therapy for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck (SCCHN) and as a single agent in recurrent or metastatic SCCHN where prior platinum-based chemotherapy has failed.

Efficacy. The efficacy of cetuximab in combination with radiation therapy versus radiation therapy alone for the treatment of SCCHN was evaluated in a randomized, controlled trial of 424 patients. For those patients randomized to cetuximab/radiation combination therapy, cetuximab was administered as a 400-mg/m² initial dose, followed by 250 mg/m² weekly for the duration of radiation therapy (6–7 wk). The main outcome measure of the trial was duration of locoregional control, and overall survival was also assessed. The median duration of locoregional control in the cetuximab/radiation treatment arm was 24.4 months compared with 14.9 months for radiation alone (HR=0.68; 95% CI, 0.52–0.89; P=.005). The median duration of overall survival in the cetuximab/radiation treatment arm was 49.0 months compared with 29.3 months for radiation alone (HR=0.74; 95% CI, 0.57–0.97; P=.03). Cetuximab therapy alone was evaluated in a single-arm trial in 103 patients with recurrent or metastatic SCCHN with documented progression within 30 days after 2–6 cycles of a platinum-based chemotherapy regimen. Patients received a 400-mg/m² initial dose followed by 250 mg/m² weekly until disease progression or unacceptable toxicity. Tumor response and progression were assessed by an Independent Radiographic Review Committee (IRC), which reported an objective response rate of 13% (95% CI, 7%–21%) and a median duration of response of 5.8 months (range, 1.2–5.8 mo).

Dosing. Premedication with an H₁ antagonist (eg, 50 mg of diphenhydramine IV) is recommended with cetuximab therapy. The recommended dose of cetuximab in combination with radiation therapy for the treatment of SCCHN is 400 mg/m² as an initial loading dose (first infusion) administered as a 120-minute IV infusion (maximum infusion rate 5 mL/min) 1 week prior to initiation of a course of radiation therapy. The recommended weekly maintenance dose (all other infusions) is 250 mg/m² infused over 60 minutes (maximum infusion rate 5 mL/min) weekly for the duration of radiation therapy (6–7 wk).