Cetuximab (1 brand name, 1 dosage form, 1 route)
Available dosage forms: VIAL.
Routes of administration: INTRAVENOUS.
Brand Names
- ERBITUX
Boxed Warning
Infusion Reactions: ERBITUX can cause serious and fatal infusion reactions [see Warnings and Precautions (5.1), Adverse Reactions (6)] . Immediately interrupt and permanently discontinue ERBITUX for serious infusion reactions [see Dosage and Administration (2.5)] . Cardiopulmonary Arrest: Cardiopulmonary arrest or sudden death occurred in patients with squamous cell carcinoma of the head and neck receiving ERBITUX with radiation therapy or a cetuximab product with platinum-based therapy and fluorouracil. Monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after ERBITUX administration [see Warnings and Precautions (5.2, 5.6)] .
Contraindications
None.
Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections of the label: Infusion reactions [see Warnings and Precautions (5.1)]. Cardiopulmonary arrest [see Warnings and Precautions (5.2)]. Pulmonary toxicity [see Warnings and Precautions (5.3)]. Dermatologic toxicity [see Warnings and Precautions (5.4)]. Hypomagnesemia and Electrolyte Abnormalities [see Warnings and Precautions (5.6)].
Mechanism of Action
The epidermal growth factor receptor (EGFR, HER1, c-ErbB-1) is a transmembrane glycoprotein that is a member of a subfamily of type I receptor tyrosine kinases including EGFR, HER2, HER3, and HER4. The EGFR is constitutively expressed in many normal epithelial tissues, including the skin and hair follicle. Expression of EGFR is also detected in many human cancers including those of the head and neck, colon, and rectum. 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 Ras proteins, but in cells with activating Ras somatic mutations, the resulting mutant Ras proteins are continuously active regardless 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. In the setting of BRAF-mutant CRC, induction of EGFR-mediated MAPK pathway activation has been identified as a mechanism of resistance to BRAF inhibitors. Combinations of a BRAF inhibitor and agents targeting EGFR have been shown to overcome this resistance mechanism in no