Erbitux (cetuximab)
Company: Imclone, Bristol-Myers Squibb
Approval Status: Approved February 2004
Treatment for: Colorectal Cancer
Areas: Gastroenterology; Oncology
| General Information | Clinical Results | Side Effects | Mechanism of Action | Literature References | Additional Information |
General Information
Erbitux (cetuximab) for injection is a monoclonal antibodyt hat targets and inhibits epidermal growth factor receptor (EGFr). EGFr is over-expressed in more than 35% of all solid malignant tumors. It is used alone or combination with other therapies for the treatment of colorectal cancer.
Erbitux is indicated, in combination with irinotecan, for the treatment of EGFR-expressing, metastatic colorectal cancer in patients who are refractory to irinotecan-based chemotherapy. In addition, it is also approved for use as a single agent in the treatment of patients with EGFR-expressing, metastatic colorectal cancer who are intolerant to irinotecan-based chemotherapy.
The recommended dosage of Erbitux is 400 mg/m2 as an initial loading dose, administered as a 120-minute IV infusion. The recommended weekly maintenance dose is 250 mg/m2 infused over 60 minutes.
Clinical Results
FDA approval of Erbitux was based on three separate clinical trials on subjects with EGFR-expressing metastatic colorectal cancer, whose disease had progressed after receiving an irinotecan-containing regimen.
A randomized, controlled trial enrolling 329 subjects investigated Erbitux both as a monotherapy and in combination with irinotecan. Subjects received Erbitux plus irinotecan or Erbitux monotherapy, administered as a 400 mg/m2 initial dose, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicity. Eighty-eight percent of subjects had baseline Karnofsky Performance Status of 80 or higher. Fifty-eight percent of subjects had colon cancer and 40% rectal cancer with two-thirds of them having previously failed oxaliplatin treatment. Data showed that the median duration of response in the overall population was 5.7 months in the combination arm and 4.2 months in the monotherapy arm. Analysis showed that subjects randomized to Erbitux and irinotecan demonstrated a significantly longer median time to disease progression compared with Erbitux alone.
An open-label, single-arm trial enrolling 138 subjects investigated Erbitux in combination with irinotecan. Subjects received a 20-mg test dose of Erbitux on day 1, followed by a 400-mg/m2 initial dose, and 250 mg/m2 weekly until disease progression or unacceptable toxicity. Seventy-four subjects had documented progression to irinotecan. Results demonstrated an overall response rate of 15% for the overall population and 12% for the irinotecan-failure population. The median durations of response were 6.5 and 6.7 months, respectively. In a third trial, Erbitux was studied as a single agent in a open-label, single-arm study enrolling 57 subjects. Results showed an overall response rate of 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.
No comments:
Post a Comment