Cetuximab - Erbitux®
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|Not applicable - DO NOT DILUTE|
| Quick Summary: Premedicate with an H1 antagonist. Administer 400 mg/m2 initial dose as a 120-minute intravenous infusion followed by 250 mg/m2 weekly infused over 60 minutes. Initiate Erbitux one week prior to initiation of radiation therapy. Reduce the infusion rate by 50% for NCI CTC Grade 1 or 2 infusion reactions and non-serious NCI CTC Grades 3–4 infusion reactions. Permanently discontinue for serious infusion reactions. Withhold infusion for severe, persistent acneform rash. Reduce dose for recurrent, severe rash.
Do not administer Erbitux as an intravenous push or bolus. Administer via infusion pump or syringe pump. Do not exceed an infusion rate of 10 mg/min. Administer through a low protein binding 0.22-micrometer in-line filter. The solution should be clear and colorless and may contain a small amount of easily visible, white, amorphous, cetuximab particulates. Do not shake or dilute.
|Stability / Miscellaneous|
Mechanism of Action
Cetuximab binds specifically to the EGFR on both normal and tumor cells, and competitively inhibits the binding of epidermal growth factor (EGF) and other ligands, such as transforming growth factor-alpha. In vitro assays and in vivo animal studies have shown that binding of cetuximab to the EGFR blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased matrix metalloproteinase and vascular endothelial growth factor production. Signal transduction through the EGFR results in activation of wild-type KRAS protein. However, in cells with activating KRAS somatic mutations, the mutant KRAS protein is continuously active and appears independent of EGFR regulation.
In vitro, cetuximab can mediate antibody-dependent cellular cytotoxicity (ADCC) against certain human tumor types. In vitro assays and in vivo animal studies have shown that cetuximab inhibits the growth and survival of tumor cells that express the EGFR. No anti-tumor effects of cetuximab were observed in human tumor xenografts lacking EGFR expression. The addition of cetuximab to radiation therapy or irinotecan in human tumor xenograft models in mice resulted in an increase in anti-tumor effects compared to radiation therapy or chemotherapy alone.
Following the recommended dose regimen (400 mg/m2 initial dose; 250 mg/m2 weekly dose), concentrations of cetuximab reached steady-state levels by the third weekly infusion with mean peak and trough concentrations across studies ranging from 168 to 235 and 41 to 85 µg/mL, respectively. The mean half-life of cetuximab was approximately 112 hours (range 63–230 hours). The pharmacokinetics of cetuximab were similar in patients with SCCHN and those with colorectal cancer.
Based on a population pharmacokinetic analysis, female patients with colorectal cancer had a 25% lower intrinsic clearance of cetuximab than male patients. Qualitatively similar, but smaller gender differences in cetuximab clearance were observed in patients with SCCHN. The gender differences in clearance do not necessitate any alteration of dosing because of a similar safety profile.
1. INDICATIONS AND USAGE
1.1 Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Erbitux, as a single agent, is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck for whom prior platinum-based therapy has failed. [See PACKAGE INSERT FOR Clinical Studies (14.1).]
1.2 Colorectal Cancer
Erbitux, in combination with irinotecan, is indicated for the treatment of EGFR-expressing metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy. The effectiveness of Erbitux in combination with irinotecan is based on objective response rates. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Erbitux in combination with irinotecan for the treatment of EGFR-expressing, metastatic colorectal carcinoma. [See PACKAGE INSERT FOR Clinical Studies (14.2) and Warnings and Precautions (5.7).]
Retrospective subset analyses of metastatic or advanced colorectal cancer trials have not shown a treatment benefit for Erbitux in patients whose tumors had KRAS mutations in codon 12 or 13. Use of Erbitux is not recommended for the treatment of colorectal cancer with these mutations [see PACKAGE INSERT FOR Clinical Studies (14.2) and Clinical Pharmacology (12.1).]
2.1 Squamous Cell Carcinoma of the Head and Neck
Erbitux in combination with radiation therapy:
2.2 Colorectal Cancer
2.3 Recommended Premedication
2.4 Dose Modifications
Immediately and permanently discontinue Erbitux for serious infusion reactions requiring medical intervention and/or hospitalization. [See PACKAGE INSERT FOR Warnings and Precautions (5.1).]
Table 1: Erbitux Dose Modification Guidelines for Rash
2.5 Preparation for Administration
Administer via infusion pump or syringe pump. Do not exceed an infusion rate of 10 mg/min.
Administer through a low protein binding 0.22-micrometer in-line filter.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
The solution should be clear and colorless and may contain a small amount of easily visible, white, amorphous, cetuximab particulates. Do not shake or dilute.
3. DOSAGE FORMS AND STRENGTHS
200 mg/100 mL, single-use vial
HOW SUPPLIED/STORAGE AND HANDLING
NDC 66733-948-23 100 mg/50 mL, single-use vial, individually packaged in a carton
Erbitux® is a registered trademark of ImClone Systems Incorporated.
|[PACKAGE INSERT DATA] : ERBITUX (cetuximab) solution. ImClone Systems Incorporated, Branchburg, NJ 08876. Revision Date March 2010.|