Erbitux (cetuximab)

Erbitux (cetuximab), in combination with radiation therapy, is a monoclonal antibody indicated for the initial treatment of locally or regionally advanced head and neck cancer of a specific type (squamous cell carcinoma).

Used alone, Erbitux is also approved to treat patients with head and neck cancers that have returned in the same location or spread to other parts of the body and for head and neck cancers that have progressed following platinum-based chemotherapy. Erbitux is also used on metastatic colorectal cancers that contain epidermal growth factor receptors.

The most common side effects of Erbitux include:

• rash,
• itching,
• dry or cracked skin,
• nail changes,
• headache,
• diarrhea,
• nausea,
• vomiting,
• upset stomach,
• weight loss,
• weakness, and
• respiratory, skin, and mouth infections.

Erbitux also can cause low blood magnesium, potassium, and calcium. Patients taking Erbitux should limit their exposure to the sun. Rare but serious side effects of Erbitux include:

• life-threatening allergic reactions and
• heart attacks, especially if the patient was also obtaining chemotherapy or radiotherapy.

Recommended Dosage For Squamous Cell Carcinoma Of The Head And Neck (SCCHN)

• The recommended initial dose is 400 mg/m² administered one week prior to initiating a course of radiation therapy or on the first day of platinum-based therapy and fluorouracil as a 120-minute intravenous infusion.
• The recommended subsequent dosage (all other infusions) is 250 mg/m² weekly as a 60-minute infusion for the duration of radiation therapy (6–7 weeks) or until disease progression or unacceptable toxicity when administered in combination with platinum-based therapy and fluorouracil.
• Complete Erbitux administration 1 hour prior to radiation therapy or platinum-based therapy with fluorouracil.

Monotherapy

• The recommended initial dose is 400 mg/m² administered as a 120-minute intravenous infusion.
• The recommended subsequent dosage (all other infusions) is 250 mg/m² weekly as a 60-minute infusion until disease progression or unacceptable toxicity.

Recommended Dosage For Colorectal Cancer (CRC)

Determine EGFR-expression status using FDA-approved tests prior to initiating treatment. Also confirm the absence of a Ras mutation prior to initiation of treatment with Erbitux. Information on FDA-approved tests for the detection of K-Ras mutations in patients with metastatic CRC is available at: http://www.fda.gov/medicaldevices/productsandmedicalprocedures/invitrodiagnostics/ucm301431.htm.

• The recommended initial dose, either as monotherapy or in combination with irinotecan or Folfiri (irinotecan, fluorouracil, leucovorin), is 400 mg/m² administered as a 120-minute intravenous infusion.
• The recommended subsequent dosage, either as monotherapy or in combination with irinotecan or Folfiri, is 250 mg/m² weekly as a 60-minute infusion until disease progression or unacceptable toxicity.
• Complete Erbitux administration 1 hour prior to irinotecan or Folfiri.

Premedication

Premedicate with a histamine-1 (H₁) receptor antagonist intravenously 30-60 minutes prior to the first dose or subsequent doses as deemed necessary.

Dosage Modifications For Adverse Reactions

Reduce, delay, or discontinue Erbitux to manage adverse reactions as described in Table 1.

Table 1: Recommended Dosage Modifications for Adverse Reactions

No Information provided

• Based on findings from animal studies and its mechanism of action, Erbitux can cause fetal harm when administered to a pregnant woman.
• There are no available data for Erbitux exposure in pregnant women.
• In an animal reproduction study, intravenous administration of cetuximab once weekly to pregnant cynomolgus monkeys during the period of organogenesis resulted in an increased incidence of embryolethality and abortion.
• Disruption or depletion of EGFR in animal models results in impairment of embryo-fetal development including effects on
  • placental,
  • lung,
  • cardiac,
  • skin, and
  • neural development.
• Human IgG is known to cross the placental barrier; therefore, cetuximab may be transmitted from the mother to the developing fetus.